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Targeting Autophagy for Cancer Treatment and Tumor Chemosensitization

Marta Pérez-Hernández, Alain Arias, David Martínez-García and 3 more

Cancers · 2019 · Review · CC BY

Abstract

Autophagy is a tightly regulated catabolic process that facilitates nutrient recycling from damaged organelles and other cellular components through lysosomal degradation. Deregulation of this process has been associated with the development of several pathophysiological processes, such as cancer and neurodegenerative diseases. In cancer, autophagy has opposing roles, being either cytoprotective or cytotoxic. Thus, deciphering the role of autophagy in each tumor context is crucial. Moreover, autophagy has been shown to contribute to chemoresistance in some patients. In this regard, autophagy modulation has recently emerged as a promising therapeutic strategy for the treatment and chemosensitization of tumors, and has already demonstrated positive clinical results in patients. In this review, the dual role of autophagy during carcinogenesis is discussed and current therapeutic strategies aimed at targeting autophagy for the treatment of cancer, both under preclinical and clinical development, are presented. The use of autophagy modulators in combination therapies, in order to overcome drug resistance during cancer treatment, is also discussed as well as the potential challenges and limitations for the use of these novel therapeutic strategies in the clinic.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 26, 2026. Paragraph numbers are ours, so an answer can point at one.

1. Introduction

1Cellular homeostasis is crucial for cell survival and refers to all processes involved in the maintenance of an internal steady state at the level of the cell. Autophagy is one of the main catabolic mechanisms that contributes to cellular homeostasis, through the degradation and recycling of cytoplasmic components and organelles in the lysosomes. This process confers the ability to adapt to environmental stresses, preventing cellular damage, and promoting cell survival, even in starving conditions, thus having a main physiologic cytoprotective role. It is a process tightly regulated and its dysfunction has been related to several pathologies, such as neurodegeneration, cancer, or aging. Hence, autophagy modulation is emerging as a promising new therapeutic strategy to treat these malignancies. Indeed, more than 120 clinical trials related to the process of autophagy were initiated to date. The majority of those target autophagy for cancer treatment, already showing promising results, for instance, using chloroquine or hydroxychloroquine as single agents or in combination therapies. Nevertheless, the role of autophagy in cancer is somewhat controversial. Cytotoxic or cytoprotective roles have been reported depending on the cellular context. Therefore, the deep understanding of autophagy regulation and the identification of its role in each cellular context is crucial for the selection of an appropriate therapeutic intervention involving autophagy modulation in cancer.

2In this review, the molecular mechanisms that regulate autophagy and the dual role of autophagy in cancer are presented and discussed. Moreover, current strategies targeting autophagy for cancer treatment are summarized, highlighting combination therapies involving autophagy modulators that can sensitize cancer cells to conventional therapies, thus being able to overcome chemoresistance.

2. Autophagy Process and Regulation

3The term autophagy encompasses diverse cellular processes that are characterized by lysosomal degradation of cytoplasmic material. Three different types of autophagy have been described: Microautophagy, chaperone mediated autophagy (CMA), and macroautophagy. Microautophagy consists of direct engulfment, via lysosomal membrane invagination, of cytoplasmic material that has to be degraded. In mammals, this process also occurs in late endosomes, which is known as endosomal microautophagy. CMA involves the targeting of specific proteins by chaperones and their delivery to lysosomes for their subsequent degradation. Finally, macroautophagy is a highly conserved process involving the formation of autophagosomes, double membrane vesicles that engulf cytoplasmic components and fuse with the lysosomes for their content degradation. A specific type of macroautophagy is called mitophagy, which consists of the selective degradation of damaged mitochondria by autophagy, promoting their turnover, and preventing the accumulation of dysfunctional mitochondria.

4Macroautophagy (here on called autophagy) has multiple steps, including the initiation, nucleation, elongation, maturation, and vesicle content degradation (Figure 1). This process is tightly regulated at the molecular level by a family of proteins called autophagy-related proteins (ATGs). The initiation step can be triggered through diverse stresses, such as growth factors or nutrient deprivation, hypoxia, oxidative stress, and protein aggregation, among others. Under starvation, low levels of glucose, amino acids, or growth factors provoke the activation of Unc-51-like kinase 1 (ULK1) complex (consisting of ULK1, ATG13, RB1-inducible coiled-coil protein 1 (FIP200) and ATG101)) through the inhibition of the mammalian target of rapamycin complex 1 (mTORC1). Similarly, low levels of ATP activate AMP-activated protein kinase (AMPK), inducing mTORC1 inhibition and subsequent ULK1 activation. Once ULK1 complex is activated (initiation step), it induces the phosphorylation and activation of the catalytic subunit of vacuolar protein sorting 34 (VPS34), a class III phosphatidylinositol 3-kinase (PI3KC3) that forms a complex with VPS15, Beclin-1, and ATG14. During the vesicle nucleation step, Beclin-1 acts as a scaffold for the rest of the components and VPS34 converts phosphatidylinositol (PI) to PI-3-phosphate (PI3P) giving rise to the phagophore, the initial portion of double membrane that will enclose the cytoplasmic material. This process takes place in the endoplasmic reticulum by the anchoring of the PI3KC3 complex through ATG14 protein to a region called omegasome. After phagophore formation, ATG7 and ATG10 mediate ATG12 conjugation to ATG5, which form a complex with ATG16L1 that attaches to to the autophagosome membrane during vesicle elongation. At the same time, microtubule-associated protein light chain 3 (LC3, also named ATG8) is cleaved by the protease ATG4 to form LC3-I, then it is activated by ATG7 and finally ATG3, at the vesicle membrane, promoting the conjugation of LC3-I (or γ-aminobutiric acid receptor-associated proteins (GABARAPs)) with membrane-resident phosphatidylethanolamine (PE) to form LC3-II that will permit cargo recognition and vesicle elongation and fusion. Apart from the endoplasmic reticulum, other compartments also act as membrane donors, such as Golgi, recycling endosomes, mitochondria, or plasma membrane. After vesicle expansion and sealing, the autophagosome maturates and fuses with the lysosome, resulting in an autophagolysosome. Several soluble N-ethylmaleimide-sensitive factor activating protein receptor (SNARE) proteins, such as syntaxin 17 (STX17) and synaptosomal-associated protein 29 (SNAP29) or the lysosome-associated membrane protein 2 (LAMP2) participate in the fusion of autophagosomes with lysosomes. Finally, acidic hydrolases coming from the lysosome degrade the autophagic cargo and the resulting products, such as amino acids or fatty acids, are finally recycled to the cytosol.

3. Dual Role of Autophagy in Cancer

5Autophagy has opposing roles in cancer, preventing tumor initiation in healthy tissues, but favoring cancer progression once the tumor is formed. Before the onset of carcinogenesis, the cytoprotective role of autophagy has been described to mainly act as a tumor suppressor mechanism, mitigating metabolic stress and genome instability that may cause tumor initiation. Indeed, loss of function of ATGs, such as Beclin-1, has been associated with increased risk of cancer. For instance, the suppression of ATG proteins in mice has been shown to provoke multiple benign tumors in liver. However, once the primary tumor is formed, the role of autophagy in cancer cells varies, being cytotoxic or cytoprotective depending on the cellular context. Therefore, it is crucial to understand the dual role of autophagy in cancer cells for the selection of a successful therapeutic strategy targeting autophagy.

6On one hand, some tumors can undergo autophagic cell death (ACD) upon the induction of autophagy by some anticancer drugs, acting as a cytotoxic process. ACD frequently occurs in cancer cells lacking functional apoptotic machinery, such as p53-deficient cancer cells. Hence, autophagy induction may be an appropriate therapeutic strategy for this type of tumors. Likewise, autophagy activation has also been described as beneficial when combined with therapies that induce immunogenic cell death, since cells dying from autophagy release certain molecules, damage-associated molecular pattern molecules (DAMPs), which recruit immune effectors enhancing the therapeutic response.

7On the other hand, some tumors trigger autophagy as a response to mitigate the cellular stress induced by an anticancer drug. In this case, inhibition of autophagy sensitizes cancer cells to therapy, enhancing the cytotoxic effects induced by chemotherapeutic agents. Indeed, autophagy has been described as a pro-survival mechanism present in most advanced tumors, facilitating tumor adaptation to different stresses, such as hypoxia or nutrient deprivation, thus mediating tumor progression. Accordingly, many types of advanced cancers show higher basal autophagic activity than normal tissues, and some have been described as “autophagy-dependent” tumors, such as pancreatic cancer or activated Ras tumors. This basal autophagy also facilitates cancer cell adaptation to therapy-induced stresses, provoking therapy resistance in these tumors, which is one of the major challenges in the clinic. Moreover, autophagy has also been related to the survival of dormant cancer cells and metastatic tumor recurrence. Hence, the inhibition of autophagy may be an appropriate therapeutic strategy to treat these tumors.

4. Therapeutic Strategies Targeting Autophagy

8Modulation of autophagy has emerged as a promising therapeutic option for cancer treatment. Due to the dual role of autophagy in cancer cells, activators as well as inhibitors have been described as feasible chemotherapeutic agents.

9In this section, we compiled different therapeutic interventions targeting autophagy, either for its stimulation or for its inhibition (Figure 1).

4.1. Autophagy Stimulation for Cancer Treatment

10Induction of ACD has become an interesting alternative to overcome resistance to apoptosis and to exploit a caspase independent cell death for cancer treatment. In the following sections, compounds for which the mechanism of action is based on stimulating autophagy are described (Table 1).

4.1.1. mTOR Inhibitors

11The mTOR is a protein kinase that participates in multiple cellular processes such as cell growth, survival, metabolism, and immunity. Thus, mTOR regulates several cellular mechanisms including cell cycle, apoptosis, and autophagy, inhibiting the initiation of the latter process. Rapamycin (sirolimus), a secondary metabolite isolated from Streptomyces hygroscopicus, showed potent antifungal, antitumor, and immunosuppressive properties. Rapamycin and its semi-synthetic analogues, known as rapalogs, are allosteric selective inhibitors of mTORC1 affecting downstream targets, including the activation of autophagy. However, their efficacy inhibiting tumor growth is limited due to lack of inhibition of mTORC2 and other compensatory signaling pathways that promote cell survival.

12Rapamycin has shown to inhibit proliferation and induce ACD in murine sarcoma, neuroblastoma, lung cancer, and osteosarcoma. Conversely, the rapalog temsirolimus or cell cycle inhibitor-779 (CCI779), has shown to inhibit tumor growth in vitro in adenoid cystic carcinoma but has also shown to stimulate autophagy as a pro-survival mechanism in renal-cell carcinoma. Additionally, everolimus (or RAD001), a derivative rapalog developed for oral administration, has shown to induce cell cycle arrest through autophagy-mediated degradation of cyclin D1 in breast cancer cells, but promotes autophagy in aromatase inhibitor-resistant breast cancer cells as a mechanism of resistance.

13Other types of mTOR inhibitors are compounds that compete with ATP, impeding phosphorylation of its target proteins, resulting in a more efficient inhibition of mTOR. Among them, AZD8055 inhibits both mTOR complexes and has shown to inhibit tumor growth and induce ACD in hepatocellular carcinoma cell lines, but it is also capable of limiting tumor growth through induction of apoptosis and cell cycle arrest. Taken together these findings suggest that mTOR inhibitors may act through different mechanisms to induce cell death in a tumor context dependent manner, which makes them suitable for combined therapies to overcome cancer cell resistance.

4.1.2. BH3 Mimetics

14BH3 (Bcl-2 homology 3) mimetics are a group of small molecules that mimic interactions of BH3-only proteins, which are a sub-group of pro-apoptotic proteins in the Bcl-2 family. In general, BH3 mimetics may stimulate autophagy by liberating Beclin-1 from Bcl2 and Bcl-XL inhibition.

15Gossypol is a BH3 mimetic isolated from cotton that has a high affinity for Bcl-2, Bcl-XL, Mcl-1, and Bcl-w. Its orally available enantiomeric form-gossypol (AT-101) has shown to induce ACD in malignant glioma, but the induced autophagy has also been accompanied by apoptosis in head and neck squamous cell carcinoma, malignant mesothelioma, and colon cancer cells. Obatoclax (GX15-070) is another BH3 mimetic that has shown autophagic-mediated necroptosis in oral squamous cell carcinoma, rhabdomyosarcoma cells, and acute lymphoblastic leukemia cells. Moreover, obatoclax induced autophagy in adenoid cystic carcinoma and Beclin-1 independent autophagy inhibition in colorectal cancer cells. Finally, ABT-737 has shown effectivity in vitro for hepatocellular carcinoma cells in a Beclin-1-dependent autophagy manner.

4.1.3. Cannabinoids

16Cannabinoids are a group of more than 60 lipophilic ligands for specific cell-surface cannabinoid receptors (CB1 y 2) present in the plant cannabis sativa, with Δ9-Tetrahydrocannabinol (THC) being the main psychoactive compound. Cannabinoids have shown potent anticancer effects related to autophagy, but they have also shown cytoprotective effects depending on cell type and cannabinoid used. THC has shown to activate non-canonical autophagy-mediated apoptosis in melanoma cells and induce ACD in glioma cells through mTORC1 inhibition and autolysosome permeabilization with the consequent release of cathepsins and posterior induction of apoptosis. JWH-015 is a synthetic cannabinoid CB2 receptor-selective agonist that has shown to inhibit tumor growth through an autophagy-dependent mechanism in hepatocellular carcinoma cells and in vivo models through inhibition of Akt/mTORC1-pathway via AMPK activation.

4.1.4. Histone Deacetylase Inhibitors (HDACIs)

17The HDAC family includes four classes (I-IV) of transcriptional repressors that alter the structure of chromatin (via deacetylation) and have been studied as anticancer compounds based on their potential to regulate gene expression. Although apoptosis has been referred to as the main route for HDACIs-induced cancer cell death, autophagy stimulation has also been implicated, being the inactivation of PI3K/Akt/mTOR signaling the most described pathway.

18Suberoylanilide hydroxamic acid (SAHA, Vorinostat) (a pan HDAC inhibitor) was the first HDACI approved by the FDA for the treatment of cutaneous T-cell lymphoma that has shown to inhibit tumor growth through autophagy stimulation via activation of Cathepsin B in breast cancer cells in vitro. Finally, MHY2256 (a synthetic class III HDAC inhibitor) has shown to induce ACD, cell cycle arrest and apoptosis in endometrial cancer cells in both in vitro and in vivo.

4.1.5. Natural Products

19Some natural compounds have shown promising anticancer activities based on autophagy stimulation. Betulinic acid is a pentacyclic triterpenoid derived from widespread plants that has shown to induce ACD in multiple myeloma cells with high levels of Bcl-2 expression. This derivative acts as an attenuator for mitochondrial-mediated apoptosis, promoting ACD by inducing Beclin-1 phosphorylation. Resveratrol, a polyphenol compound widely found in plants, has been shown to inhibit cell proliferation in breast cancer stem-like cells via suppressing the Wnt/b-catenin signaling pathway. This pathway, which regulates critical genes in tissue development and homeostasis, is aberrantly activated in many cancers and its inhibition has been reported to be related with autophagy processes. δ-Tocotrienol is one of the four isomers that comprises vitamin E that has shown cytotoxic effects against prostate cancer cells in vitro through autophagy activation via ER stress. Curcumin is a major constituent of Curcuma longa (turmeric) that induces autophagy, which has been shown to elicit a dual role protecting or leading to cell death depending on the duration of the treatment and concentration used.

4.1.6. Others

20Other compounds have been reported to induce ACD in cancer. For example, lapatinib is a small molecule tyrosine kinase inhibitor, targeting epidermal growth factor receptors that is capable of inducing ACD in hepatocellular carcinoma and in acute leukemia cell lines. APO866 is an inhibitor of nicotinamide adenine dinucleotide (NAD) biosynthesis that has shown anticancer activity through induction of ACD in cells from hematological malignancies.

4.2. Autophagy Inhibition for Cancer Treatment

21In several tumors, autophagy has a protective role; therefore, its inhibition could be an interesting approach for tumor treatment. There are several autophagy inhibitors that block the process of autophagy at different steps, which we detail below (Table 2).

4.2.1. ULK Inhibitors

22ULKs are a family of serine/threonine protein kinases that form complexes with multiple regulator units. The role of ULK1 is essential for the initiation of autophagy, however the role of ULK2 in autophagy seems to be cell type dependent. Due to the homology between ULK1 and ULK2, inhibitors of ULK1 also inhibit ULK2. ULK1 has been shown to be upregulated in several cancers, which correlated with poor prognosis and treatment resistance. Inhibition of ULK1 has been shown to induce a decrease in tumor growth and induction of apoptosis. This has led to the search for compounds that inhibit this kinase activity finding some molecules that compete with the ATP-binding site, such as compound 6, MRT68921, and MRT67307. Besides them, SBI-0206965 is the most studied, which inhibits autophagy and induces apoptosis in neuroblastoma cell lines, non-small cell lung cancer (NSCLC) cells, and in clear cell renal carcinoma cells. Moreover, it has also been reported to be a direct inhibitor of AMPK, which is a serine/threonine kinase that activates the ULK complex, among other roles. Recently more ULK inhibitors, such as ULK100 and ULK101, have been described, which supports that the idea that blocking ULK1 may be a good strategy for cancer therapy.

4.2.2. Pan PI3K Inhibitors

23The family of phosphoinositide 3-kinases (PI3Ks) is divided into three classes with different substrate preferences, which define their functions. The role of class II on autophagy is unclear. However, class I activates mTORC1 through the PI3K/Akt pathway and consequently inhibits autophagy, while class III (VPS34) activates autophagy. PI3K pathways have been associated with cancer due to their participation in tumorigenic processes such as cell proliferation, survival, migration, and angiogenesis. Therefore, they are a good target for therapy development. Most of the studied PI3K inhibitors are not selective for a specific class of PI3K, hence, they affect different cellular processes, not only autophagy, and consequently their effect cannot be only attributed to inhibition of autophagy. However, due to their therapeutic relevance, we describe briefly some of them below.

243-Methyladenine (3MA) was one of the first inhibitors of autophagy described. It exerts a dual effect on autophagy. Under starving conditions it suppresses autophagy through PI3KC3 inhibition. However, in the presence of nutrients it promotes autophagy by inhibition of PI3KC1. Additionally, it has been reported that it reduces the expression of drug efflux transporters, overcoming taxol and doxorubicin resistance. 3MA is effective at high concentrations, although presents solubility problems. In order to overcome this limitation some derivatives have been synthetized. Wortmannin is a fungal metabolite that binds irreversibly to the catalytic site of PI3Ks. LY294002 is a synthetic small molecule with poor solubility and short half-life. A conjugate analog of LY294002, named SF1126, was designed to accumulate in integrin expressing tissues, improving LY294002 solubility and pharmacokinetic, favoring its accumulation in the tumor site and showing antitumor and antiangiogenic properties in mouse models. Other non-selective Pan PI3K inhibitors are PI103, KU55933, Gö6976, and GSK1059615.

4.2.3. VPS34 (PI3KC3) Complex Inhibitors

25VPS34 is a PI3KC3 that transforms PI to PI3P. VPS34 forms a complex with several subunits needed for its activation, such as VPS15 (also known as p150), ATG14, and Beclin-1. Autophagy can be blocked by inhibition of VPS34 activity; SAR405 is one compound of the (2S)-tetrahydropyrimido-pyrimidinones series with kinase inhibitor activity by strong competition for ATP site. However, it is highly selective for PI3KC3, compared to class I and II, and more than 200 protein kinases and 15 lipid kinases. SAR405 inhibits autophagy induced either by starvation or mTOR inhibition. VPS34-IN1 is a bipyrimidinamine that inhibits PI3KC3 selectively, compared with more than 300 protein kinases analyzed. Additionally, PIK-III, a bisaminopyrimidine, binds to a hydrophobic pocket unique in VPS34 that cannot be found in other related kinases. Compound 31 is a small molecule selective against protein and other lipid kinases. All these four inhibitors are selective for PI3KC3, but it should be noted that VPS34 can form different complexes with other subunits that lead to a different localization and function, participating also in vesicle trafficking. Thus, inhibitors of VPS34 can also have an effect on endosomal trafficking, as the case of SAR405 that prevents the activity of both VPS34 complexes. Therefore, it may also affect cellular secretion.

26On the other hand, autophagy can be also inhibited blocking PI3KC3 complex formation; Spautin-1 indirectly inhibits the activity of VPS34 by proteosomal degradation of proteins that form VPS34 complexes through reduction of Beclin-1 deubiquitination mediated by USP10 and USP13.

4.2.4. ATG inhibitors

27Membrane PI3P produced by VPS34 leads to the recruitment of PI3P-binding ATG proteins and additional factors, resulting in the formation of complexes that participate in the elongation of the phagophore. Inhibition of autophagy can be achieved by impeding the formation of these complexes.

28ATG7 participates in the formation of the complex ATG12-ATG5 and the conjugation of PE to LC3 and GABARAP. Recently, some inhibitors of ATG7 (WO2018/089786) have been designed and it has extended the use of micro RNAs that target ATG7 gene such as miR-154 that inhibits blade cancer progression.

29On the other hand, ATG4B cleaves LC3, activating it for its conjugation with PE necessary for the expansion of the autophagosome and its recognition. Additionally, it participates in LC3-PE deconjugation, which is important for LC3 recycling and for the fusion of the autophagosome with the lysosome. Therefore, ATG4B could be a good target to inhibit autophagy more selectively, thus, a large number of ATG4B possible inhibitors have been screened in the last years. NSC185058 is a small compound that docked at the active site of ATG4B inhibiting not only autophagy but also the volume of the autophagosomes, which is accompanied by suppression of tumor growth in an osteosarcoma subcutaneous mouse model. Tioconazole is an antifungal drug that binds to the active site of ATG4 blocking autophagy flux reducing cell viability and sensitizing tumor cells to doxorubicin in a xenograft mouse model. Other ATG4B inhibitors that suppress autophagy in cell lines and in vivo inhibiting cell proliferation are UAMC-2526, a derivative of benzotropolones stable in plasma, and LV-320, a styrylquinoline.

30It should be noticed that the roles of ATG4B in cancer are not well understood and some of the ATG4 inhibitors showed only inhibition in LC3-PE delipidation, but not in the autophagosome formation such as S130 and FMK-9a. Additionally, some studies are focused on the evaluation of different markers that may predict the effectiveness of those inhibitors. For instance, ATG4B inhibition is effective only in Her-2 positive cells and not in those negative.

4.2.5. Autophagosome Formation Inhibition

31Verteporfin is a benzoporphyrin derivative used in the clinic in photodynamic therapy. Interestingly, it prevents autophagosome formation induced by glucose and serum deprivation, but not by mTOR inhibition. One possible mechanism of action of verteporfin is the blockade of p62 oligomerization, a protein necessary for the sequestration of ubiquitinated targets into autophagosomes. Additional to autophagy inhibition, verteporfin reduces transcriptional co-activators that regulate the Hippo pathway, implicated in cell growth and stem cell function. Verteporfin inhibits cell proliferation, angiogenesis, and migration, and induces apoptosis. It inhibits autophagy in vivo but has no effect as a single agent in tumor growth. However, it moderately sensitizes tumor cells to cytotoxic agents.

4.2.6. Lysosome Inhibitors

32The last step in autophagy is the fusion of autophagosomes with lysosomes, whose hydrolases degrade the autophagosome content. The inhibition of autophagy at this point consists of the use of lysosomal inhibitors.

33Chloroquine (CQ) and its analog hydroxychloroquine (HCQ) are drugs used for the treatment of various diseases, such as malaria and more recently cancer. They are weak bases and the unprotonated form of CQ/HCQ can diffuse through cell membranes and enter into organelles such as lysosomes, where the high concentration of H+ induces their protonation and consequently increases lysosomal pH. Once CQ/HCQ are protonated, they are trapped in the lysosomes producing an increase of their volume, and inhibiting the activity of lysosomal enzymes.

34CQ and HCQ are the only autophagy inhibitors approved for clinical use. Although short-term CQ/HCQ treatment has been considered safe, retinopathy has been reported produced by long-term treatment with HCQ in about 7.5% of patients and cardiotoxicity. The prevalence depends on the dosage and the duration of treatment. This toxicity limitation, along with inconsistencies in the results obtained in the clinic, have led to the study of new and more potent autophagy inhibitors. Thus, CQ analogs that exert more potent autophagy inhibitory activity have been synthetized. Lys05 is a dimeric analog of CQ that accumulates within acidic organelles, including lysosomes, more potently than HCQ. DQ661, a dimeric quinacrine (DQ), not only inhibits lysosomal catabolism, including autophagy, but also targets palmitoyl-protein thioesterase-1, resulting in the inhibition of mTORC1 signaling. DQ661 has shown effects on tumor mouse models alone and it also overcame resistance to gemcitabine. Another antimalaria compound found to inhibit autophagy with antitumoral properties is VATG-027. On the other hand, mefloquine is also accumulated in lysosomes disrupting autophagy, it induces apoptosis and inhibits multidrug resistance protein1 (MDR1) being effective in multidrug-resistant tumor cells. Mefloquine sensitizes chronic myeloid leukemia (CML) cells derived from patients in chronic phase to TK inhibitors showing selectivity for stem/progenitor tumoral cells to normal cells.

35CQ and its derivatives are not the only drugs that target lysosomes to inhibit autophagy; GLP (ganoderma lucidum polysaccharide) is a polysaccharide from the fungus Ganoderma lucidium with multiple antitumoral properties. GLP induces apoptosis in cancer cell lines and reduces tumor growth in mouse models. It has recently been seen that GLP impairs autophagy flux by reduction of lysosome acidification and the accumulation of autophagosomes has suggested to be the cause of apoptosis induction. Bafilomycin A (BafA) is a vacuolar-H+ ATPase inhibitor that disrupts the acidification of lysosomes, vesicles, and vacuoles by preventing the entry of H+ into these organelles. BafA also inhibits the fusion of autophagosomes with lysosomes, by disruption of Ca2+ gradients implied in this process.

36Ionophores can also disrupt lysosomal pH, impairing the autophagy process. Tambjamine analogues are anion selective ionophores derived from the naturally occurring tambjamines and induce mitochondrial swelling and autophagy blockade with cytotoxic effects in lung cancer cells and cancer stem cells (CSCs). Monensin, nigericin, and lasalocid are cation ionophores, but only monensin presents selectivity for lysosomes. Squaramides are synthetic chloride transporters that also induce cell death by apoptosis.

37On the other hand, the WX8-family comprises five chemical analogs that disrupt the fusion of lysosomes with autophagosomes, lysosomes fission, and sequestration of molecules into the lysosomes without altering their pH. These compounds bind to PIKFYVE phosphoinositide kinase and present potent antitumoral effects on autophagic dependent cells. Vacuolin-1 activates RAB5A blocking the fusion of the autophagosomes with lysosomes, however it also inhibits the fusion of endosomes with lysosomes, resulting in a general endosomal-lysosomal degradation defective.

38Clomipramine (CM) is a FDA-approved prodrug for the treatment of psychiatric disorders the metabolite of which, desmethylclomipramine (DCMI), impairs autophagic flux blocking lysosomal degradation that sensitizes tumor cells to cancer treatment. DCMI also affects lung CSCs. Additionally, protease inhibitors can also inhibit the lysosomal degradation, such as pepstatin A (aspartyl proteases; cathepsin D and E), Leupeptin and E64d (cysteine proteases; cathepsin B, H, and L). On the other hand, nanoparticles are usually accumulated into lysosomes by endocytosis internalization, which may cause lysosome impairment. Gold nanoparticles and nanodiamonds have shown to inhibit autophagy by disruption of lysosomal function, which sensitizes tumors to arsenical base therapy.

39Several studies have suggested that the anti-tumor effects of lysosomal inhibitors may be independent of autophagy inhibition since they also interfere in other cellular mechanisms producing non-autophagy related effects. Remarkably, disruption of the lysosomes not only blocks autophagy, but lysosomal permeabilization releases proteases such as cathepsins that are active at cytosolic pH and participate in apoptosis and apoptosis-like and necrosis-like cell death. Additionally, lysosomes also participate in tumor invasion, hence, these inhibitors have shown to be effective against metastasis, targeting cancer stem cells, and inducing tumor vessel normalization.

40As mentioned above, there are efforts to find genetic determinants to sensitivity or resistance to these lysosomal inhibitors. Metastatic cells are more vulnerable to CQ and BafA, suggesting that patients with metastasis could benefit from those treatments. Morgan and coworkers also showed a relationship between the expression of ID4 and metastatic potential. Additionally, overexpression of helicase-like transcription factor (HLTF) seems to be related with the resistance to HCQ, Lys05 and BafA treatment and tumors with the V600E mutation in BRAF (v-Raf murine sarcoma viral oncogene homolog B) present cytoprotective autophagy.

5. Autophagy Modulation for Tumor Sensitization to Anticancer Therapies

41It has been accepted that chemotherapy, as well as radiotherapy, could activate autophagy. This opens the possibility that modulation of autophagy may enhance sensitivity to these cancer treatments. In this section, we highlight some combination therapies that use compounds that target autophagy-inducing sensitization of cancer cells to anticancer therapies.

5.1. Autophagy Modulation to Overcome Radio-Resistance

42One of the first-line treatments for many types of cancers is radiotherapy. The combination of autophagy inhibitors and radiation therapy has shown improved anti-tumor effects in cancer treatment. For instance, the ATG4B inhibitor NSC185058 and CQ enhance the antitumor effect of radiotherapy in glioblastoma. Furthermore, non-cytotoxic amounts of CQ enhanced the radiation sensitivity in bladder cancer cell lines.

43The activation of autophagy also radiosensitizes the cells and this effect is increased in the presence of apoptosis inhibitors. Thus, combination therapies based on autophagy stimulation have been formulated to overcome radioresistance in some tumors. For example, YCW1, an optimized HDACI, enhances radiosensitivity in breast cancer cells inducing ER stress and increasing autophagy. Similar results have been reached using a combination of radiotherapy, THC, and cannabidiol in glioma and gossypol in glioblastoma multiforme.

44As mentioned before, the effect of autophagy after radiation is not uniform in all types of tumors; it can be cytoprotective, non-cytoprotective, or have a cytotoxic effect. Hence, the efforts should be focused on the determination of some markers that could predict the effect of autophagy modulators in combination with radiotherapy. For instance, the expression of p53 has been suggested to be determinant for a radiosensitization effect of CQ and p18-CycE (proteolytic cyclin E fragment). Nrf2 antioxidant pathway seems to be involved in autophagy-induced radioresistance, which is reversed by 3MA co-treatment. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) loss is associated with radio and chemoresistance, and activation of autophagy by rapamycin induces cytotoxic autophagy that overcomes radioresistance.

45It should be noted that the models used to analyze these radiosensitization effects are of major importance in order to obtain feasible results. For instance, inhibition of autophagy combined with radiotherapy in immunodeficient mice has a sensitization effect; however, in immunocompetent mice it promotes tumor growth.. This opposite effect is due to the role of autophagy in the immunogenic antitumor response. Therefore, these types of studies should be performed in an immunocompetent context.

5.2. Autophagy Modulation to Overcome Chemoresistance

46Inhibition of autophagy may sensitize tumor cells to common drugs or may overcome the resistance acquired by those cells to chemotherapeutic agents. In this section, we highlight some of the most recent and relevant findings in combining different antitumor drugs with autophagy inhibitors and some activators.

47CQ and HCQ potentiate the cytotoxicity of multiple drugs such as 5-fluorouracil, cisplatin, and temozolomide. Moreover, combination treatment with CQ and trastuzumab completely suppressed tumor growth by >90% in a HER2-positive breast cancer tumor xenograft completely refractory to trastuzumab.

48Additionally other autophagy inhibitors have shown interesting results; verteporfin increased the potential of gemcitabine in an in vitro model of pancreatic cancer. SBI-0206965 overcame resistance to cisplatin in NSCLC cells and to cabozantinib in metastatic colorectal cancer. The combination of celecoxib, a specific inhibitor of cyclooxygenase-2, with CQ and SAR405 resulted in higher cell death, and 3MA also enhanced cell death induced by bortezomib in glioblastoma cell lines. Moreover, the combination of the CQ analog lys05 with the second generation of tyrosin kinase inhibitor, nilotinib, has shown an additive effect in the reduction of the number of leukemia stem cells in CML mouse models. UAMC-2526 potentiates the effect of oxaliplatin in colorectal cancer xenograft mouse model by inhibition of autophagy, and tumors treated with UAMC-2526 also showed a more differentiated phenotype.

49The combination of autophagy activators and inhibitors together have also been studied; CQ and HCQ potentiate the effect of mTOR inhibitors, such as temsirolimus or everolimus in colorectal cancer cells, melanoma, and neuroendocrine neoplasms, showing inhibition of autophagy as a mechanism to overcome resistance to mTOR inhibitors. In addition, CQ has also demonstrated to improve anticancer effects of vorinostat, as well as a combination of everolimus and SAR405 showed synergy. These results would make one think that the inhibition of autophagy is a better therapeutic approach because autophagy presents a protective role in these models. However, although to a lesser extent, autophagy activators are also able to overcome chemoresistance. Temsirolimus has demonstrated to potentiate the activity of gemcitabine and cisplatin in bladder cancer cell lines and also decrease the resistance of colon cancer cells to cetuximab. Similarly, curcumin has shown to enhance gefitinib effect on primary gefitinib-resistant small-cell lung cancer cells through an autophagy-dependent synergism.

50Nevertheless, in some cases, autophagy modulation has shown controversial results in preclinical studies. For instance, it has been shown in vitro that SBI-0206965, an ULK1 inhibitor, induces apoptosis in combination with mTOR inhibitors in A549 cells. However, in neuroblastoma cells, SBI-0206965 sensitizes cells to TNF-Related Apoptosis Inducing Ligand (TRAIL) treatment but not to mTOR inhibitors indicating the non-protective role of autophagy in this model. At this point, it would be necessary to use molecular markers that could predict the response of the tumors to autophagy modulators, such as v-Raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutation, which has been associated with protective autophagy.

51Finally, the development of nanotechnology exploits tumor-targeting therapy directing multiple drugs to the tumor mass, including autophagy inhibitors, which have been encapsulated in different nanocarrier systems to obtain more efficient therapies. On one hand, HCQ nanoencapsulation showed more efficacy than free HCQ. On the other, these multiplatform systems allow the combination of autophagy inhibitors with other chemotherapeutic agents, diagnosis system, or other therapeutic approaches, such as sonodynamic or photothermal therapy, showing efficient tumor suppression effect. Additionally, CQ may be used to promote the accumulation of the drugs in the tumor site; pretreatment with CQ affects macrophages endocytic capacity, which limits nanoparticle accumulation in the liver, reducing liver clearance, and improves tumor microcirculation, which promotes co-delivery of antitumoral drugs in tumors.

52All of the above suggest that modulation of autophagy may be a promising approach to overcome radio and chemoresistance. However, more efforts are needed to predict the response of patients to those treatments.

6. Combination Therapy in Clinical Trials

53Inhibition and activation of autophagy for cancer treatment has been evaluated in the clinic and clinical trials with autophagy modulators that present results are compiled in Table 3.

54CQ and HCQ have been included in 21 and 66 clinical trials for cancer treatment, respectively, 17 of which are currently active and 24 have been completed. In summary, HCQ has limited activity as a single agent, despite the fact that it inhibits autophagy in patients with different early-stage solid tumors. However, the analysis of autophagy in patients with metastatic pancreatic adenocarcinoma showed inconsistent inhibition and no significant therapeutic efficacy. The inhibition of autophagy in combination therapies of HCQ with anticancer agents such as gemcitabine, temozolomide, and bortezomib has been corroborated. However, efficacy results with these and other chemotherapeutic agents, such as erlotinib, were negligible or moderate. Additionally, the combination of HCQ with chemotherapy and radiotherapy at the same time inhibited autophagy in 45–66% of patients and this combination did not improve the overall survival rate. Patients with glioblastoma that had received radiotherapy and chemotherapy were treated for 12 months with CQ showing limited results; however, chronic administration of CQ improved the overall survival rate about 50%. Additionally, the combination of radiotherapy with CQ did not improve the overall response rate in patients with brain metastasis.

55All these results show inconsistency not only at the level of autophagy inhibition but also in the efficacy outcome of this therapy. As mentioned before, the role of autophagy is context dependent, and this has been proven in the clinic. For instance, CQ overcame resistance to vemurafenib, a BRAF inhibitor, in different patients with BRAFV600E-mutant brain tumors. However, this combination showed no synergistic effect on patients without this mutation. This points out the importance of the identification of patients that are most likely to respond to this combination therapy.

56Regarding autophagy activators,-gossypol in combination with cisplatin and etoposide has shown promising results on phase I clinical trial for small cell lung cancer. However, its combination with docetaxel or androgen deprivation therapy have not demonstrated enough efficacy on phase II clinical trial for head and neck cancer or metastatic prostate cancer. Vorinostat in combination with tamoxifen showed moderate response with 40% of response or stable disease in patients with hormone-therapy resistant breast cancer.

57Finally, the combination of autophagy activators and inhibitors, such as the combination of vorinostat with HCQ has shown promising results. Although rapalog temsirolimus is not powerful enough to be used as a single agent for the treatment of breast and renal carcinoma, the combination of HCQ with rapamycin showed a moderate positive response. Moreover, HCQ combined with rapamycin in metronomic chemotherapy showed encouraging results with 40% of partial response and 84% control of disease. Finally, combination of HCQ and temsirolimus also showed stabilization of the disease in 67–74% of the patients with a consistent inhibition of autophagy.

7. Conclusions

58Targeting autophagy for cancer treatment seems to be a promising therapeutic strategy, although significant challenges remain to be addressed in order to improve the therapeutic results obtained in the clinic. In particular, since the outcome of modulating autophagy depends on the tumor context, it must be carefully defined which patients would benefit from which treatment before starting any therapeutic intervention.

59Autophagy suppresses tumor initiation in healthy tissues, showing a cytoprotective role. Hence, the modulation of autophagy through autophagy activators might be beneficial in patients with an increased risk of developing cancers. On the other hand, once the tumor is formed, activating autophagy will induce ACD in some tumors, provoking their reduction. This strategy may be especially relevant in apoptosis-resistant tumors. Nevertheless, autophagy has a protective role in other tumors, especially those called “autophagy-dependent”; hence, the inhibition of autophagy would induce therapeutic effects in those patients. Indeed, inhibition of autophagy at early or late stages leads to different consequences; prevention of the autophagosome formation may neutralize the protective role of autophagy, sensitizing cells to chemotherapeutic agents, being a good strategy for combination regimens. Conversely, lysosomotropic agents produce autophagy vacuoles accumulation, leading to cellular stress and a consequent cytotoxic effect, being able to reduce the tumor in single therapy.

60This review underscore the double-edged-sword role of autophagy in cancer; hence, a deeper understanding on how autophagy affects cancer progression, the search of appropriate biomarkers to identify the responder patient population to a defined autophagy modulator, and clear and suitable pharmacodynamic markers to monitor patients’ responses are eagerly needed to improve success in clinical studies with autophagy modulators.

References 273

1.
Deter R.L., Baudhuin P., Duve C. de Participation of lysosomes in cellular autophagy induced in rat liver by glucagon. J. Cell Biol. 1967;35:11-16.
Not in our library10.1083/jcb.35.2.c11
2.
Mizushima N. Autophagy: Process and function. Genes Dev. 2007;21:2861-2873.
Not in our library10.1101/gad.1599207
3.
Mizushima N., Levine B., Cuervo A.M., Klionsky D.J. Autophagy fights disease through cellular self-digestion. Nature. 2008;451:1069-1075.
Not in our library10.1038/nature06639
4.
Dikic I., Elazar Z. Mechanism and medical implications of mammalian autophagy. Nat. Rev. Mol. Cell Biol. 2018;19:349-364.
Not in our library10.1038/s41580-018-0003-4
5.
Targeting Autophagy in Cancer: Update on Clinical Trials and Novel Inhibitors · 2017
No notice
6.
U.S. National Library of Medicine of Clinical Trials.
Not in our library
7.
White E. The role for autophagy in cancer (White, 2015).pdf. J. Clin. Investig. 2015;125:42-46.
Not in our library10.1172/jci73941
8.
Galluzzi L., Baehrecke E.H., Ballabio A., Boya P., Bravo-San Pedro J.M., Cecconi F., Choi A.M., Chu C.T., Codogno P., Colombo M.I., et al. Molecular definitions of autophagy and related processes. EMBO J. 2017;36:1811-1836.
Not in our library10.15252/embj.201796697
9.
Li W.W., Li J., Bao J.K. Microautophagy: Lesser-known self-eating. Cell. Mol. Life Sci. 2012;69:1125-1136.
Not in our library10.1007/s00018-011-0865-5
10.
Sahu R., Kaushik S., Clement C.C., Cannizzo E.S., Scharf B., Follenzi A., Potolicchio I., Nieves E., Cuervo A.M., Santambrogio L. Microautophagy of Cytosolic Proteins by Late Endosomes. Dev. Cell. 2011;20:131-139.
Not in our library10.1016/j.devcel.2010.12.003
11.
Kaushik S., Cuervo A.M. Chaperone-mediated autophagy: A unique way to enter the lysosome world. Trends Cell Biol. 2012;22:407-417.
Not in our library10.1016/j.tcb.2012.05.006
12.
Xu H.-M., Hu F. The role of autophagy and mitophagy in cancers. Arch. Physiol. Biochem. 2019;1-9.
Not in our library10.1080/13813455.2019.1675714
13.
Tsukada M., Ohsumi Y. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS. 1993;333:169-174.
Not in our library10.1016/0014-5793(93)80398-e
14.
The mammalian ULK1 complex and autophagy initiation · 2017
No notice
15.
Hosokawa N., Hara T., Kaizuka T., Kishi C., Takamura A., Miura Y., Iemura S., Natsume T., Takehana K., Yamada N., et al. Nutrient-dependent mTORC1 Association with the ULK1–Atg13–FIP200 Complex Required for Autophagy. Mol. Biol. Cell. 2009;20:1981-1991.
Not in our library10.1091/mbc.e08-12-1248
16.
Kim J., Kundu M., Viollet B., Guan K.L. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat. Cell Biol. 2011;13:132-141.
Not in our library10.1038/ncb2152
17.
Noda T., Matsunaga K., Yoshimori T. Atg14L recruits PtdIns 3-kinase to the ER for autophagosome formation. Autophagy. 2011;7:438-439.
Not in our library10.4161/auto.7.4.14679
18.
Lystad A.H., Carlsson S.R., de la Ballina L.R., Kauffman K.J., Nag S., Yoshimori T., Melia T.J., Simonsen A. Distinct functions of ATG16L1 isoforms in membrane binding and LC3B lipidation in autophagy-related processes. Nat. Cell Biol. 2019;21:372-383.
Not in our library10.1038/s41556-019-0274-9
19.
Nguyen T.N., Padman B.S., Usher J., Oorschot V., Ramm G., Lazarou M. Atg8 family LC3/GAB ARAP proteins are crucial for autophagosome-lysosome fusion but not autophagosome formation during PINK1/Parkin mitophagy and starvation. J. Cell Biol. 2016;215:857-874.
Not in our library10.1083/jcb.201607039
20.
Hamasaki M., Furuta N., Matsuda A., Nezu A., Yamamoto A., Fujita N., Oomori H., Noda T., Haraguchi T., Hiraoka Y., et al. Autophagosomes form at ER-mitochondria contact sites. Nature. 2013;495:389-393.
Not in our library10.1038/nature11910
21.
Nascimbeni A.C., Giordano F., Dupont N., Grasso D., Vaccaro M.I., Codogno P., Morel E. ER–plasma membrane contact sites contribute to autophagosome biogenesis by regulation of local PI3P synthesis. EMBO J. 2017;36:2018-2033.
Not in our library10.15252/embj.201797006
22.
Itakura E., Kishi-Itakura C., Mizushima N. The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes/lysosomes. Cell. 2012;151:1256-1269.
Not in our library10.1016/j.cell.2012.11.001
23.
LAMP-2 is required for incorporating syntaxin-17 into autophagosomes and for their fusion with lysosomes · 2016
Not checked
24.
Karantza-Wadsworth V., Patel S., Kravchuk O., Chen G., Mathew R., Jin S., White E. Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev. 2007;21:1621-1635.
Not in our library10.1101/gad.1565707
25.
Jin S., White E. Tumor suppression by autophagy through the management of metabolic stress. Autophagy. 2008;4:563-566.
Not in our library10.4161/auto.5830
26.
Liang X.H., Jackson S., Seaman M., Brown K., Kempkes B., Hibshoosh H., Levine B. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature. 1999;402:672-676.
Not in our library10.1038/45257
27.
Qu X., Yu J., Bhagat G., Furuya N., Hibshoosh H., Troxel A., Rosen J., Eskelinen E., Mizushima N., Ohsumi Y., et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J. Clin. Investig. 2003;112:1809-1820.
Not in our library10.1172/jci20039
28.
Takamura A., Komatsu M., Hara T., Sakamoto A., Kishi C., Waguri S., Eishi Y., Hino O., Tanaka K., Mizushima N. Autophagy-deficient mice develop multiple liver tumors. Genes Dev. 2011;25:795-800.
Not in our library10.1101/gad.2016211
29.
Fulda S. Autophagy in Cancer Therapy. Front. Oncol. 2017;7:1-4.
Not in our library10.3389/fonc.2017.00128
30.
Denton D., Kumar S. Autophagy-dependent cell death. Cell Death Differ. 2019;26:605-616.
Not in our library10.1038/s41418-018-0252-y
31.
Shimizu S., Nakao K., Minato N., Uemoto S. Autophagic Cell Death and Cancer Chemotherapeutics. Innovative Medicine. 2015;219-226.
Not in our library
32.
Michaud M., Martins I., Sukkurwala A.Q., Adjemian S., Ma Y., Pellegatti P., Shen S., Kepp O., Scoazec M., Mignot G., et al. Autophagy-Dependent Anticancer Immune Responses Induced by Chemotherapeutic Agents in Mice. Science (80-.). 2011;334:1573-1578.
Not in our library10.1126/science.1208347
33.
Follo C., Cheng Y., Richards W.G., Bueno R., Broaddus V.C. Autophagy facilitates the release of immunogenic signals following chemotherapy in 3D models of mesothelioma. Mol. Carcinog. 2019;58:1754-1769.
Not in our library10.1002/mc.23050
34.
Shimgu T., Fujiwara K., Bogler O., Akiyama Y., Meritake K., Shinojima N., Tamacla Y., Yokoyama T., Kondo S. Inhibition of autophagy at a late stage enhances imatinib-induced cytotoxicity In human malignant glioma cells. Int. J. Cancer. 2009;124:1060-1071.
Not in our library10.1002/ijc.24030
35.
Liu D., Yang Y., Liu Q., Wang J. Inhibition of autophagy by 3-MA potentiates cisplatin-induced apoptosis in esophageal squamous cell carcinoma cells. Med. Oncol. 2011;28:105-111.
Not in our library10.1007/s12032-009-9397-3
36.
Selvakumaran M., Amaravadi R.K., Vasilevskaya I.A., O’Dwyer P.J. Autophagy inhibition sensitizes colon cancer cells to antiangiogenic and cytotoxic therapy. Clin. Cancer Res. 2013;19:2995-3007.
Not in our library10.1158/1078-0432.ccr-12-1542
37.
Zheng L., Li H., Mo Y., Qi G., Liu B., Zhao J. Autophagy inhibition sensitizes LY3023414-induced anti-glioma cell activity in vitro and in vivo. Oncotarget. 2017;8:98964-98973.
Not in our library10.18632/oncotarget.22147
38.
Guo J.Y., Xia B., White E. Autophagy-Mediated tumor Promotion. Cell. 2013;155:1216-1219.
Not in our library10.1016/j.cell.2013.11.019
39.
Gammoh N., Fraser J., Puente C., Syred H.M., Kang H., Ozawa T., Lam D., Acosta J.C., Finch A.J., Holland E., et al. Suppression of autophagy impedes glioblastoma development and induces senescence. Autophagy. 2016;12:1431-1439.
Not in our library10.1080/15548627.2016.1190053
40.
Guo J.Y., Chen H.Y., Mathew R., Fan J., Strohecker A.M., Karsli-Uzunbas G., Kamphorst J.J., Chen G., Lemons J.M.S., Karantza V., et al. Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes Dev. 2011;25:460-470.
Not in our library10.1101/gad.2016311
41.
Yang S., Wang X., Contino G., Liesa M., Sahin E., Ying H., Bause A., Li Y., Stommel J.M., Dell’Antonio G., et al. Pancreatic cancers require autophagy for tumor growth. Genes Dev. 2011;25:717-729.
Not in our library10.1101/gad.2016111
42.
Autophagy promotes the survival of dormant breast cancer cells and metastatic tumour recurrence · 2018
No notice
43.
Shi H., Zhang L., Zhang C., Hao Y., Zhao X. Rapamycin may inhibit murine S180 sarcoma growth by regulating the pathways associated with autophagy and cancer stem cells. J. Cancer Res. Ther. 2019;15:398-403.
Not in our library10.4103/jcrt.jcrt_639_18
44.
Lin X., Han L., Weng J., Wang K., Chen T. Rapamycin inhibits proliferation and induces autophagy in human neuroblastoma cells. Biosci. Rep. 2018;38:1-8.
Not in our library10.1042/bsr20181822
45.
Jiang R.Y., Pei H.L., Gu W.D., Huang J., Wang Z.G. Autophagic inhibitor attenuates rapamycin-induced inhibition of proliferation in cultured A549 lung cancer cells. Eur. Rev. Med. Pharmacol. Sci. 2014;18:806-810.
Not in our library
46.
Xie Z.G., Xie Y., Dong Q.R. Inhibition of the mammalian target of rapamycin leads to autophagy activation and cell death of MG63 osteosarcoma cells. Oncol. Lett. 2013;6:1465-1469.
Not in our library10.3892/ol.2013.1531
47.
Liu W., Huang S., Chen Z., Wang H., Wu H., Zhang D. Temsirolimus, the mTOR inhibitor, induces autophagy in adenoid cystic carcinoma: In vitro and in vivo. Pathol. Res. Pract. 2014;210:764-769.
Not in our library10.1016/j.prp.2014.03.008
48.
Singla M., Bhattacharyya S. Autophagy as a potential therapeutic target during epithelial to mesenchymal transition in renal cell carcinoma: An in vitro study. Biomed. Pharmacother. 2017;94:332-340.
Not in our library10.1016/j.biopha.2017.07.070
49.
Chen G., Ding X.-F., Bouamar H., Pressley K., Sun L.-Z. Everolimus induces G 1 cell cycle arrest through autophagy-mediated protein degradation of cyclin D1 in breast cancer cells. Am. J. Physiol. Physiol. 2019;317:C244-C252.
Not in our library10.1152/ajpcell.00390.2018
50.
Lui A., New J., Ogony J., Thomas S., Lewis-Wambi J. Everolimus downregulates estrogen receptor and induces autophagy in aromatase inhibitor-resistant breast cancer cells. BMC Cancer. 2016;16:1-15.
Not in our library10.1186/s12885-016-2490-z
51.
Chresta C.M., Davies B.R., Hickson I., Harding T., Cosulich S., Critchlow S.E., Vincent J.P., Ellston R., Jones D., Sini P., et al. AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity. Cancer Res. 2010;70:288-298.
Not in our library10.1158/0008-5472.can-09-1751
52.
Hu M., Huang H., Zhao R., Li P., Li M., Miao H., Chen N., Chen M. AZD8055 induces cell death associated with autophagy and activation of AMPK in hepatocellular carcinoma. Oncol. Rep. 2014;31:649-656.
Not in our library10.3892/or.2013.2890
53.
Benvenuto M., Mattera R., Masuelli L., Taffera G., Andracchio O., Tresoldi I., Lido P., Giganti M.G., Godos J., Modesti A., et al. (±)-Gossypol induces apoptosis and autophagy in head and neck carcinoma cell lines and inhibits the growth of transplanted salivary gland cancer cells in BALB/c mice. Int. J. Food Sci. Nutr. 2017;68:298-312.
Not in our library10.1080/09637486.2016.1236077
54.
Effect of the BH3 Mimetic Polyphenol (–)-Gossypol (AT-101) on the in vitro and in vivo Growth of Malignant Mesothelioma · 2018
Not checked
55.
Lan L., Appelman C., Smith A.R., Yu J., Larsen S., Marquez R.T., Liu H., Wu X., Gao P., Roy A., et al. Natural product (-)-gossypol inhibits colon cancer cell growth by targeting RNA-binding protein Musashi-1. Mol. Oncol. 2015;9:1406-1420.
Not in our library10.1016/j.molonc.2015.03.014
56.
Voss V., Senft C., Lang V., Ronellenfitsch M.W., Steinbach J.P., Seifert V., Kögel D. The pan-Bcl-2 inhibitor (-)-gossypol triggers autophagic cell death in malignant glioma. Mol. Cancer Res. 2010;8:1002-1016.
Not in our library10.1158/1541-7786.mcr-09-0562
57.
Sulkshane P., Teni T. BH3 mimetic Obatoclax (GX15-070) mediates mitochondrial stress predominantly via MCL-1 inhibition and induces autophagy-dependent necroptosis in human oral cancer cells. Oncotarget. 2017;8:60060-60079.
Not in our library10.18632/oncotarget.11085
58.
Basit F., Cristofanon S., Fulda S. Obatoclax (GX15-070) triggers necroptosis by promoting the assembly of the necrosome on autophagosomal membranes. Cell Death Differ. 2013;20:1161-1173.
Not in our library10.1038/cdd.2013.45
59.
Bonapace L., Bornhauser B.C., Schmitz M., Cario G., Ziegler U., Niggli F.K., Schäfer B.W., Schrappe M., Stanulla M., Bourquin J.P. Induction of autophagy-dependent necroptosis is required for childhood acute lymphoblastic leukemia cells to overcome glucocorticoid resistance. J. Clin. Investig. 2010;120:1310-1323.
Not in our library10.1172/jci39987
60.
Yao X., Li X., Zhang D., Xie Y., Sun B., Li H., Sun L., Zhang X. B-cell lymphoma 2 inhibitor ABT-737 induces Beclin1- and reactive oxygen species-dependent autophagy in Adriamycin-resistant human hepatocellular carcinoma cells. Tumor Biol. 2017;39:1-12.
Not in our library10.1177/1010428317695965
61.
Armstrong J.L., Hill D.S., McKee C.S., Hernandez-Tiedra S., Lorente M., Lopez-Valero I., Anagnostou M.E., Babatunde F., Corazzari M., Redfern C.P.F., et al. Exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death. J. Investig. Dermatol. 2015;135:1629-1637.
Not in our library10.1038/jid.2015.45
62.
Dihydroceramide accumulation mediates cytotoxic autophagy of cancer cells via autolysosome destabilization · 2016
No notice
63.
Salazar M., Carracedo A., Salanueva Í.J., Hernández-Tiedra S., Lorente M., Egia A., Vázquez P., Blázquez C., Torres S., García S., et al. Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. J. Clin. Investig. 2009;119:1359-1372.
Not in our library10.1172/jci37948
64.
Vara D., Salazar M., Olea-Herrero N., Guzmán M., Velasco G., Díaz-Laviada I. Anti-tumoral action of cannabinoids on hepatocellular carcinoma: Role of AMPK-dependent activation of autophagy. Cell Death Differ. 2011;18:1099-1111.
Not in our library10.1038/cdd.2011.32
65.
Han H., Li J., Feng X., Zhou H., Guo S., Zhou W. Autophagy-related genes are induced by histone deacetylase inhibitor suberoylanilide hydroxamic acid via the activation of cathepsin B in human breast cancer cells. Oncotarget. 2017;8:53352-53365.
Not in our library10.18632/oncotarget.18410
66.
De U., Son J.Y., Sachan R., Park Y.J., Kang D., Yoon K., Lee B.M., Kim I.S., Moon H.R., Kim H.S. A new synthetic histone deacetylase inhibitor, MHY2256, induces apoptosis and autophagy cell death in endometrial cancer cells via p53 acetylation. Int. J. Mol. Sci. 2018;19:2743.
Not in our library10.3390/ijms19092743
67.
Zhou H., Luo W., Zeng C., Zhang Y., Wang L., Yao W., Nie C. PP2A mediates apoptosis or autophagic cell death in multiple myeloma cell lines. Oncotarget. 2017;8:80770-80789.
Not in our library10.18632/oncotarget.20415
68.
Resveratrol Inhibits Breast Cancer Stem-Like Cells and Induces Autophagy via Suppressing Wnt/β-Catenin Signaling Pathway · 2014
No notice
69.
Fontana F., Moretti R.M., Raimondi M., Marzagalli M., Beretta G., Procacci P., Sartori P., Montagnani Marelli M., Limonta P. δ-Tocotrienol induces apoptosis, involving endoplasmic reticulum stress and autophagy, and paraptosis in prostate cancer cells. Cell Prolif. 2019;52:1-15.
Not in our library10.1111/cpr.12576
70.
Deng Q., Liang L., Liu Q., Duan W., Jiang Y., Zhang L. Autophagy is a major mechanism for the dual effects of curcumin on renal cell carcinoma cells. Eur. J. Pharmacol. 2018;826:24-30.
Not in our library10.1016/j.ejphar.2018.02.038
71.
Chen Y.J., Chi C.W., Su W.C., Huang H.L. Lapatinib induces autophagic cell death and inhibits growth of human hepatocellular carcinoma. Oncotarget. 2014;5:4845-4854.
Not in our library10.18632/oncotarget.2045
72.
Chen Y.J., Fang L.W., Su W.C., Hsu W.Y., Yang K.C., Huang H.L. Lapatinib induces autophagic cell death and differentiation in acute myeloblastic leukemia. Onco. Targets. Ther. 2016;9:4453-4464.
Not in our library10.2147/ott.s105664
73.
Ginet V., Puyal J., Rummel C., Aubry D., Breton C., Cloux A.J., Majjigapu S.R., Sordat B., Vogel P., Bruzzone S., et al. A critical role of autophagy in antileukemia/lymphoma effects of APO866, an inhibitor of NAD biosynthesis. Autophagy. 2014;10:603-617.
Not in our library10.4161/auto.27722
74.
Targeting mTOR for cancer therapy · 2019
No notice
75.
Noda T., Ohsumi Y. Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J. Biol. Chem. 1998;273:3963-3966.
Not in our library10.1074/jbc.273.7.3963
76.
Sehgal S.N., Baker H., Vézina C. Rapamycin (Ay-22,989), a New Antifungal Antibiotic. II. Fermentation, Isolation and Characterization. J. Antibiot. (Tokyo). 1975;28:727-732.
Not in our library10.7164/antibiotics.28.727
77.
Vézina C., Kudelski A., Sehgal S.N. Rapamycin (AY 22,989) A NEW ANTIFUNGAL ANTIBIOTIC. J. Antibiot. (Tokyo). 1975;28:721-726.
Not in our library10.7164/antibiotics.28.721
78.
Pattingre S., Espert L., Biard-Piechaczyk M., Codogno P. Regulation of macroautophagy by mTOR and Beclin 1 complexes. Biochimie. 2008;90:313-323.
Not in our library10.1016/j.biochi.2007.08.014
79.
Benjamin D., Colombi M., Moroni C., Hall M.N. Rapamycin passes the torch: A new generation of mTOR inhibitors. Nat. Rev. Drug Discov. 2011;10:868-880.
Not in our library10.1038/nrd3531
80.
Chiarini F., Evangelisti C., Lattanzi G., McCubrey J.A., Martelli A.M. Advances in understanding the mechanisms of evasive and innate resistance to mTOR inhibition in cancer cells. Biochim. Biophys. Acta. Mol. Cell Res. 2019;1866:1322-1337.
Not in our library10.1016/j.bbamcr.2019.03.013
81.
Mao B., Gao S., Weng Y., Zhang L., Zhang L. Design, synthesis, and biological evaluation of imidazo[1,2-b]pyridazine derivatives as mTOR inhibitors. Eur. J. Med. Chem. 2017;129:135-150.
Not in our library10.1016/j.ejmech.2017.02.015
82.
Chen Y., Lee C.H., Tseng B.Y., Tsai Y.H., Tsai H.W., Yao C.L., Tseng S.H. AZD8055 exerts antitumor effects on colon cancer cells by inhibiting mTOR and cell-cycle progression. Anticancer Res. 2018;38:1445-1454.
Not in our library10.21873/anticanres.12369
83.
Carew J.S., Kelly K.R., Nawrocki S.T. Mechanisms of mTOR inhibitor resistance in cancer therapy. Target. Oncol. 2011;6:17-27.
Not in our library10.1007/s11523-011-0167-8
84.
Merino D., Kelly G.L., Lessene G., Wei A.H., Roberts A.W., Strasser A. BH3-Mimetic Drugs: Blazing the Trail for New Cancer Medicines. Cancer Cell. 2018;34:879-891.
Not in our library10.1016/j.ccell.2018.11.004
85.
Opydo-Chanek M., Gonzalo O., Marzo I. Multifaceted anticancer activity of BH3 mimetics: Current evidence and future prospects. Biochem. Pharmacol. 2017;136:12-23.
Not in our library10.1016/j.bcp.2017.03.006
86.
Czabotar P.E., Lessene G., Strasser A., Adams J.M. Control of apoptosis by the BCL-2 protein family: Implications for physiology and therapy. Nat. Rev. Mol. Cell Biol. 2014;15:49-63.
Not in our library10.1038/nrm3722
87.
Liang L.Z., Ma B., Liang Y.J., Liu H.C., Zhang T.H., Zheng G.S., Su Y.X., Liao G.Q. Obatoclax induces Beclin 1- and ATG5-dependent apoptosis and autophagy in adenoid cystic carcinoma cells. Oral Dis. 2015;21:470-477.
Not in our library10.1111/odi.12305
88.
Koehler B.C., Jassowicz A., Scherr A.L., Lorenz S., Radhakrishnan P., Kautz N., Elssner C., Weiss J., Jaeger D., Schneider M., et al. Pan-Bcl-2 inhibitor Obatoclax is a potent late stage autophagy inhibitor in colorectal cancer cells independent of canonical autophagy signaling. BMC Cancer. 2015;15:1-11.
Not in our library10.1186/s12885-015-1929-y
89.
Śledziński P., Zeyland J., Słomski R., Nowak A. The current state and future perspectives of cannabinoids in cancer biology. Cancer Med. 2018;7:765-775.
Not in our library10.1002/cam4.1312
90.
Costa L., Amaral C., Teixeira N., Correia-Da-Silva G., Fonseca B.M. Cannabinoid-induced autophagy: Protective or death role? Prostaglandins Other Lipid Mediat. 2016;122:54-63.
Not in our library10.1016/j.prostaglandins.2015.12.006
91.
Mrakovcic M., Kleinheinz J., Fröhlich L.F. Histone deacetylase inhibitor-induced autophagy in tumor cells: Implications for p53. Int. J. Mol. Sci. 2017;18:1883.
Not in our library10.3390/ijms18091883
92.
Newbold A., Falkenberg K.J., Prince H.M., Johnstone R.W. How do tumor cells respond to HDAC inhibition? FEBS J. 2016;283:4032-4046.
Not in our library10.1111/febs.13746
93.
Mrakovcic M., Bohner L., Hanisch M., Fröhlich L.F. Epigenetic targeting of autophagy via HDAC inhibition in tumor cells: Role of p53. Int. J. Mol. Sci. 2018;19:3952.
Not in our library10.3390/ijms19123952
94.
Mann B.S., Johnson J.R., Cohen M.H., Justice R., Pazdur R. FDA Approval Summary: Vorinostat for Treatment of Advanced Primary Cutaneous T-Cell Lymphoma. Oncologist. 2007;12:1247-1252.
Not in our library10.1634/theoncologist.12-10-1247
95.
Wang J., Ren X.R., Piao H., Zhao S., Osada T., Premont R.T., Mook R.A., Morse M.A., Lyerly H.K., Chen W. Niclosamide-induced Wnt signaling inhibition in colorectal cancer is mediated by autophagy. Biochem. J. 2019;476:535-546.
Not in our library10.1042/bcj20180385
96.
Lazarus M.B., Novotny C.J., Shokat K.M. Structure of the human autophagy initiating kinase ULK1 in complex with potent inhibitors. ACS Chem. Biol. 2015;10:257-261.
Not in our library10.1021/cb500835z
97.
Skah S., Richartz N., Duthil E., Gilljam K.M., Bindesbøll C., Naderi E.H., Eriksen A.B., Ruud E., Dirdal M.M., Simonsen A., et al. cAMP-mediated autophagy inhibits DNA damage-induced death of leukemia cells independent of p53. Oncotarget. 2018;9:30434-30449.
Not in our library10.18632/oncotarget.25758
98.
Pharmacological Inhibition of ULK1 Kinase Blocks Mammalian Target of Rapamycin (mTOR)-dependent Autophagy · 2015
Corrected
99.
Lu J., Zhu L., Zheng L.P., Cui Q., Zhu H.H., Zhao H., Shen Z.J., Dong H.Y., Chen S.S., Wu W.Z., et al. Overexpression of ULK1 Represents a Potential Diagnostic Marker for Clear Cell Renal Carcinoma and the Antitumor Effects of SBI-0206965. EBioMedicine. 2018;34:85-93.
Not in our library10.1016/j.ebiom.2018.07.034
100.
Dower C.M., Bhat N., Gebru M.T., Chen L., Wills C.A., Miller B.A., Wang H.-G. Targeted Inhibition of ULK1 Promotes Apoptosis and Suppresses Tumor Growth and Metastasis in Neuroblastoma. Mol. Cancer Ther. 2018;17:2365-2376.
Not in our library10.1158/1535-7163.mct-18-0176
101.
Tang F., Hu P., Yang Z., Xue C., Gong J., Sun S., Shi L., Zhang S., Li Z., Yang C., et al. SBI0206965, a novel inhibitor of Ulk1, suppresses non-small cell lung cancer cell growth by modulating both autophagy and apoptosis pathways. Oncol. Rep. 2017;37:3449-3458.
Not in our library10.3892/or.2017.5635
102.
Egan D.F., Chun M.G.H., Vamos M., Zou H., Rong J., Miller C.J., Lou H.J., Raveendra-Panickar D., Yang C.-C., Sheffler D.J., et al. Small molecule inhibition of the autophagy kinase ULK1 and identification of ULK1 substrates. Mol. Cell. 2015;59:285-297.
Not in our library10.1016/j.molcel.2015.05.031
103.
Martin K.R., Celano S.L., Solitro A.R., Gunaydin H., Scott M., O’Hagan R.C., Shumway S.D., Fuller P., MacKeigan J.P. A Potent and Selective ULK1 Inhibitor Suppresses Autophagy and Sensitizes Cancer Cells to Nutrient Stress. iScience. 2018;8:74-84.
Not in our library10.1016/j.isci.2018.09.012
104.
Seglen P.O., Gordon P.B. 3-Methyladenine: Specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc. Natl. Acad. Sci. USA. 1982;79:1889-1892.
Not in our library10.1073/pnas.79.6.1889
105.
Wu Y.T., Tan H.L., Shui G., Bauvy C., Huang Q., Wenk M.R., Ong C.N., Codogno P., Shen H.M. Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase. J. Biol. Chem. 2010;285:10850-10861.
Not in our library10.1074/jbc.m109.080796
106.
Zou Z., Zhang J., Zhang H., Liu H., Li Z., Cheng D., Chen J., Liu L., Ni M., Zhang Y., et al. 3-Methyladenine can depress drug efflux transporters via blocking the PI3K-AKT-mTOR pathway thus sensitizing MDR cancer to chemotherapy. J. Drug Target. 2014;22:839-848.
Not in our library10.3109/1061186x.2014.936870
107.
Wu Y., Wang X., Guo H., Zhang B., Zhang X.B., Shi Z.J., Yu L. Synthesis and screening of 3-MA derivatives for autophagy inhibitors. Autophagy. 2013;9:595-603.
Not in our library10.4161/auto.23641
108.
Powis G., Bonjouklian R., Berggren M.M., Gallegos A., Abraham R., Ashendel C., Zalkow L., Matter W.F., Dodge J., Grindey G., et al. Wortmannin, a Potent and Selective Inhibitor of Phosphatidylinositol-3-kinase. Cancer Res. 1994;54:2419-2423.
Not in our library
109.
Thelen M., Wymann M.P., Langen H. Wortmannin binds specifically to 1-phosphatidylinositol 3-kinase while inhibiting guanine nucleotide-binding protein-coupled receptor signaling in neutrophil leukocytes. Proc. Natl. Acad. Sci. USA. 1994;91:4960-4964.
Not in our library10.1073/pnas.91.11.4960
110.
Vlahos C.J., Matter W.F., Hui K.Y., Brown R.F. A Specific Inhibitor of Phosphatidylinositol 3 Kinase, 2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J. Biol. Chem. 1994;269:5241-5248.
Not in our library
111.
Garlich J.R., De P., Dey N., Jing D.S., Peng X., Miller A., Murali R., Lu Y., Mills G.B., Kundra V., et al. A vascular targeted pan phosphoinositide 3-kinase inhibitor prodrug, SF1126, with antitumor and antiangiogenic activity. Cancer Res. 2008;68:206-215.
Not in our library10.1158/0008-5472.can-07-0669
112.
Qin A., Li Y., Zhou L., Xing C., Lu X. Dual PI3K-BRD4 Inhibitor SF1126 Inhibits Colorectal Cancer Cell Growth in Vitro and in Vivo. Cell. Physiol. Biochem. 2019;52:758-768.
Not in our library10.33594/000000053
113.
Ronan B., Flamand O., Vescovi L., Dureuil C., Durand L., Fassy F., Bachelot M.F., Lamberton A., Mathieu M., Bertrand T., et al. A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy. Nat. Chem. Biol. 2014;10:1013-1019.
Not in our library10.1038/nchembio.1681
114.
Farkas T., Daugaard M., Jäättelä M. Identification of small molecule inhibitors of phosphatidylinositol 3-kinase and autophagy. J. Biol. Chem. 2011;286:38904-38912.
Not in our library10.1074/jbc.m111.269134
115.
Xie J., Li Q., Ding X., Gao Y. GSK1059615 kills head and neck squamous cell carcinoma cells possibly via activating mitochondrial programmed necrosis pathway. Oncotarget. 2017;8:50814-50823.
Not in our library10.18632/oncotarget.15135
116.
Bei S., Li F., Li H., Li J., Zhang X., Sun Q., Feng L. Inhibition of gastric cancer cell growth by a PI3K-mTOR dual inhibitor GSK1059615. Biochem. Biophys. Res. Commun. 2019;511:13-20.
Not in our library10.1016/j.bbrc.2019.02.032
117.
Characterization of VPS34-IN1, a selective inhibitor of Vps34, reveals that the phosphatidylinositol 3-phosphate-binding SGK3 protein kinase is a downstream target of class III phosphoinositide 3-kinase · 2014
No notice
118.
Dowdle W.E., Nyfeler B., Nagel J., Elling R.A., Liu S., Triantafellow E., Menon S., Wang Z., Honda A., Pardee G., et al. Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo. Nat. Cell Biol. 2014;16:1069-1079.
Not in our library10.1038/ncb3053
119.
Pasquier B., El-Ahmad Y., Filoche-Rommé B., Dureuil C., Fassy F., Abecassis P.Y., Mathieu M., Bertrand T., Benard T., Barrière C., et al. Discovery of (2 S)-8-[(3 R)-3-Methylmorpholin-4-yl]-1-(3-methyl-2-oxobutyl)-2-(trifluoromethyl)-3,4-dihydro-2 H -pyrimido[1,2- a ]pyrimidin-6-one: A novel potent and selective inhibitor of Vps34 for the treatment of solid tumors. J. Med. Chem. 2015;58:376-400.
Not in our library10.1021/jm5013352
120.
Liu J., Xia H., Kim M., Xu L., Li Y., Zhang L., Cai Y., Norberg H.V., Zhang T., Furuya T., et al. Beclin1 Controls the Levels of p53 by Regulating the Deubiquitination Activity of USP10 and USP13. Cell. 2011;147:223-234.
Not in our library10.1016/j.cell.2011.08.037
121.
Zhang J., Mao S., Wang L., Zhang W., Zhang Z., Guo Y., Wu Y., Yi F., Yao X. MicroRNA-154 functions as a tumor suppressor in bladder cancer by directly targeting ATG7. Oncol. Rep. 2019;41:819-828.
Not in our library10.3892/or.2018.6879
122.
Akin D., Wang S.K., Habibzadegah-Tari P., Law B., Ostrov D., Li M., Yin X.M., Kim J.S., Horenstein N., Dunn W.A. A novel ATG4B antagonist inhibits autophagy and has a negative impact on osteosarcoma tumors. Autophagy. 2014;10:2021-2035.
Not in our library10.4161/auto.32229
123.
Liu P.-F., Hsu C.-J., Tseng H.-H., Wu C.-H., Shu C.-W., Tsai K.-L., Yang L.-W., Tsai W.-L., Cheng J.-S., Chang H.-W., et al. Drug repurposing screening identifies tioconazole as an ATG4 inhibitor that suppresses autophagy and sensitizes cancer cells to chemotherapy. Theranostics. 2018;8:830-845.
Not in our library10.7150/thno.22012
124.
Kurdi A., Cleenewerck M., Vangestel C., Lyssens S., Declercq W., Timmermans J.P., Stroobants S., Augustyns K., De Meyer G.R.Y., Van Der Veken P., et al. ATG4B inhibitors with a benzotropolone core structure block autophagy and augment efficiency of chemotherapy in mice. Biochem. Pharmacol. 2017;138:150-162.
Not in our library10.1016/j.bcp.2017.06.119
125.
Bosc D., Vezenkov L., Bortnik S., An J., Xu J., Choutka C., Hannigan A.M., Kovacic S., Loo S., Clark P.G.K., et al. A new quinoline-based chemical probe inhibits the autophagy-related cysteine protease ATG4B OPEN. Sci. Rep. 2018;8:11653.
Not in our library10.1038/s41598-018-29900-x
126.
Fu Y., Hong L., Xu J., Zhong G., Gu Q., Gu Q., Guan Y., Zheng X., Dai Q., Luo X., et al. Discovery of a small molecule targeting autophagy via ATG4B inhibition and cell death of colorectal cancer cells in vitro and in vivo. Autophagy. 2019;15:295-311.
Not in our library10.1080/15548627.2018.1517073
127.
Qiu Z., Kuhn B., Aebi J., Lin X., Ding H., Zhou Z., Xu Z., Xu D., Han L., Liu C., et al. Discovery of Fluoromethylketone-Based Peptidomimetics as Covalent ATG4B (Autophagin-1) Inhibitors. ACS Med. Chem. Lett. 2016;7:802-806.
Not in our library10.1021/acsmedchemlett.6b00208
128.
Xu D., Xu Z., Han L., Liu C., Zhou Z., Qiu Z., Lin X., Tang G., Shen H., Aebi J., et al. Identification of new ATG4B inhibitors based on a novel high-throughput screening platform. SLAS Discov. 2017;22:338-347.
Not in our library10.1177/1087057116639202
129.
Chu J., Fu Y., Xu J., Zheng X., Gu Q., Luo X., Dai Q., Zhang S., Liu P., Hong L., et al. ATG4B inhibitor FMK-9a induces autophagy independent on its enzyme inhibition. Arch. Biochem. Biophys. 2018;644:29-36.
Not in our library10.1016/j.abb.2018.03.001
130.
Donohue E., Tovey A., Vogl A.W., Arns S., Sternberg E., Young R.N., Roberge M. Inhibition of autophagosome formation by the benzoporphyrin derivative verteporfin. J. Biol. Chem. 2011;286:7290-7300.
Not in our library10.1074/jbc.m110.139915
131.
Liu-Chittenden Y., Huang B., Shim J.S., Chen Q., Lee S.-J., Anders R.A., Liu J.O., Pan D. Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP. Genes Dev. 2012;26:1300-1305.
Not in our library10.1101/gad.192856.112
132.
Donohue E., Thomas A., Maurer N., Manisali I., Zeisser-Labouebe M., Zisman N., Anderson H.J., Ng S.S.W., Webb M., Bally M., et al. The Autophagy Inhibitor Verteporfin Moderately Enhances the Antitumor Activity of Gemcitabine in a Pancreatic Ductal Adenocarcinoma Model. J. Cancer. 2013;4:585-596.
Not in our library10.7150/jca.7030
133.
Lui J.W., Xiao S., Ogomori K., Hammarstedt J.E., Little E.C., Lang D. The efficiency of verteporfin as a therapeutic option in pre-clinical models of melanoma. J. Cancer. 2019;10:1-10.
Not in our library10.7150/jca.27472
134.
Poole B., Ohkuma S. Effect of weak bases on the intralysosomal pH in mouse peritoneal macrophages. J. Cell Biol. 1981;90:665-669.
Not in our library10.1083/jcb.90.3.665
135.
Solomon V.R., Lee H. Chloroquine and its analogs: A new promise of an old drug for effective and safe cancer therapies. Eur. J. Pharmacol. 2009;625:220-233.
Not in our library10.1016/j.ejphar.2009.06.063
136.
Shi T.T., Yu X.X., Yan L.J., Xiao H.T. Research progress of hydroxychloroquine and autophagy inhibitors on cancer. Cancer Chemother. Pharmacol. 2017;79:287-294.
Not in our library10.1007/s00280-016-3197-1
137.
McAfee Q., Zhang Z., Samanta A., Levi S.M., Ma X.-H., Piao S., Lynch J.P., Uehara T., Sepulveda A.R., Davis L.E., et al. Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency. Proc. Natl. Acad. Sci. USA. 2012;109:8253-8258.
Not in our library10.1073/pnas.1118193109
138.
Baquero P., Dawson A., Mukhopadhyay A., Kuntz E.M., Mitchell R., Olivares O., Ianniciello A., Scott M.T., Dunn K., Nicastri M.C., et al. Targeting quiescent leukemic stem cells using second generation autophagy inhibitors. Leukemia. 2019;33:981-994.
Not in our library10.1038/s41375-018-0252-4
139.
Rebecca V.W., Nicastri M.C., Mclaughlin N., Fennelly C., Ronghe A., Nofal M., Lim C., Witze E., Chude C.I., Zhang G., et al. A unified approach to targeting the lysosome’s degradative and growth signaling roles. Cancer Discov. 2017;7:1266-1283.
Not in our library10.1158/2159-8290.cd-17-0741
140.
Goodall M.L., Wang T., Martin K.R., Kortus M.G., Kauffman A.L., Trent J.M., Gately S., MacKeigan J.P. Development of potent autophagy inhibitors that sensitize oncogenic BRAF V600E mutant melanoma tumor cells to vemurafenib. Autophagy. 2014;10:1120-1136.
Not in our library10.4161/auto.28594
141.
Lam Yi H., Than H., Sng C., Cheong M.A., Chuah C., Xiang W. Lysosome Inhibition by Mefloquine Preferentially Enhances the Cytotoxic Effects of Tyrosine Kinase Inhibitors in Blast Phase Chronic Myeloid Leukemia. Transl. Oncol. 2019;12:1221-1228.
Not in our library10.1016/j.tranon.2019.06.001
142.
Sharma N., Thomas S., Golden E.B., Hofman F.M., Chen T.C., Petasis N.A., Schönthal A.H., Louie S.G. Inhibition of autophagy and induction of breast cancer cell death by mefloquine, an antimalarial agent. Cancer Lett. 2012;326:143-154.
Not in our library10.1016/j.canlet.2012.07.029
143.
Cheng S., Sliva D. Ganoderma lucidum for cancer treatment: We are close but still not there. Integr. Cancer Ther. 2015;14:249-257.
Not in our library10.1177/1534735414568721
144.
Autophagic flux disruption contributes to Ganoderma lucidum polysaccharide-induced apoptosis in human colorectal cancer cells via MAPK/ERK activation · 2019
No notice
145.
Wu K., Na K., Chen D., Wang Y., Pan H., Wang X. Effects of non-steroidal anti-inflammatory drug-activated gene-1 on Ganoderma lucidum polysaccharides-induced apoptosis of human prostate cancer PC-3 cells. Int. J. Oncol. 2018;53:2356-2368.
Not in our library10.3892/ijo.2018.4578
146.
Yamamoto A., Tagawa Y., Yoshimori T., Moriyama Y., Masaki R., Tashiro Y. Bafilomycin Ai Prevents Maturation of Autophagic Vacuoles by Inhibiting Fusion between Autophagosomesand Lysosomesin Rat HepatomaCell Line. Cell Struct. Funct. 1998;23:33-42.
Not in our library10.1247/csf.23.33
147.
Bowman E.J., Siebers A., Altendorf K. Bafilomycins; A class of inhibitors of membrane ATPases from microorganisms, animal cells, and plant cells. Proc. Natl. Acad. Sci. USA. 1988;85:7972-7976.
Not in our library10.1073/pnas.85.21.7972
148.
Mauvezin C., Neufeld T.P. Bafilomycin A1 disrupts autophagic flux by inhibiting both V-ATPase-dependent acidification and Ca-P60A/SERCA-dependent autophagosome-lysosome fusion. Autophagy. 2015;11:1437-1438.
Not in our library10.1080/15548627.2015.1066957
149.
Rodilla A.M., Korrodi-Gregório L., Hernando E., Manuel-Manresa P., Quesada R., Pérez-Tomás R., Soto-Cerrato V. Synthetic tambjamine analogues induce mitochondrial swelling and lysosomal dysfunction leading to autophagy blockade and necrotic cell death in lung cancer. Biochem. Pharmacol. 2017;126:23-33.
Not in our library10.1016/j.bcp.2016.11.022
150.
Grinde B. Effect of carboxylic ionophores on lysosomal protein degradation in rat hepatocytes. Exp. Cell Res. 1983;149:27-35.
Not in our library10.1016/0014-4827(83)90377-4
151.
Busschaert N., Park S.H., Baek K.H., Choi Y.P., Park J., Howe E.N.W., Hiscock J.R., Karagiannidis L.E., Marques I., Félix V., et al. A synthetic ion transporter that disrupts autophagy and induces apoptosis by perturbing cellular chloride concentrations. Nat. Chem. 2017;9:667-675.
Not in our library10.1038/nchem.2706
152.
Sharma G., Guardia C.M., Roy A., Vassilev A., Saric A., Griner L.N., Marugan J., Ferrer M., Bonifacino J.S., DePamphilis M.L. A family of PIKFYVE inhibitors with therapeutic potential against autophagy-dependent cancer cells disrupt multiple events in lysosome homeostasis. Autophagy. 2019;15:1694-1718.
Not in our library10.1080/15548627.2019.1586257
153.
Lu Y., Dong S., Hao B., Li C., Zhu K., Guo W., Wang Q., Cheung K.-H., Wong C.W.M., Wu W.-T., et al. Vacuolin-1 potently and reversibly inhibits autophagosome-lysosome fusion by activating RAB5A. Autophagy. 2014;10:1895-1905.
Not in our library10.4161/auto.32200
154.
Rossi M., Munarriz E.R., Bartesaghi S., Milanese M., Dinsdale D., Guerra-Martin M.A., Bampton E.T.W., Glynn P., Bonanno G., Knight R.A., et al. Desmethylclomipramine induces the accumulation of autophagy markers by blocking autophagic flux. J. Cell Sci. 2009;122:3330-3339.
Not in our library10.1242/jcs.048181
155.
Libby P., Goldberg A.L. Leupeptin, a protease inhibitor, decreases protein degradation in normal and diseased muscles. Science (80-. ). 1978;199:534-536.
Not in our library10.1126/science.622552
156.
Tanida I., Minematsu-Ikeguchi N., Ueno T., Kominami E. Lysosomal turnover, but not a cellular level, of endogenous LC3 is a marker for autophagy. Autophagy. 2005;1:84-91.
Not in our library10.4161/auto.1.2.1697
157.
Autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity · 2012
No notice
158.
Ma X., Wu Y., Jin S., Tian Y., Zhang X., Zhao Y., Yu L., Liang X.J. Gold nanoparticles induce autophagosome accumulation through size-dependent nanoparticle uptake and lysosome impairment. ACS Nano. 2011;5:8629-8639.
Not in our library10.1021/nn202155y
159.
Cui Z., Zhang Y., Xia K., Yan Q., Kong H., Zhang J., Zuo X., Shi J., Wang L., Zhu Y., et al. Nanodiamond autophagy inhibitor allosterically improves the arsenical-based therapy of solid tumors. Nat. Commun. 2018;9:4347.
Not in our library10.1038/s41467-018-06749-2
160.
Chen S., Wang C., Yeo S., Liang C.C., Okamoto T., Sun S., Wen J., Guan J.L. Distinct roles of autophagy-dependent and -independent functions of FIP200 revealed by generation and analysis of a mutant knock-in mouse model. Genes Dev. 2016;30:856-869.
Not in our library10.1101/gad.276428.115
161.
Mercer C.A., Kaliappan A., Dennis P.B. A novel, human Atg13 binding protein, Atg101, interacts with ULK1 and is essential for macroautophagy. Autophagy. 2009;5:649-662.
Not in our library10.4161/auto.5.5.8249
162.
Lee E.J., Tournier C. The requirement of uncoordinated 51-like kinase 1 (ULK1) and ULK2 in the regulation of autophagy. Autophagy. 2011;7:689-695.
Not in our library10.4161/auto.7.7.15450
163.
Chaikuad A., Koschade S.E., Stolz A., Zivkovic K., Pohl C., Shaid S., Ren H., Lambert L.J., Cosford N.D.P., Brandts C.H., et al. Conservation of structure, function and inhibitor binding in UNC-51-like kinase 1 and 2 (ULK1/2). Biochem. J. 2019;2:BCJ20190038.
Not in our library10.1042/bcj20190038
164.
Yun M., Bai H.Y., Zhang J.X., Rong J., Weng H.W., Zheng Z.S., Xu Y., Tong Z.T., Huang X.X., Liao Y.J., et al. ULK1: A promising biomarker in predicting poor prognosis and therapeutic response in human nasopharygeal carcinoma. PLoS ONE. 2015;10:e0117375.
Not in our library10.1371/journal.pone.0117375
165.
Zou Y., Chen Z., He X., He X., Wu X., Chen Y., Wu X., Wang J., Lan P. High expression levels of unc-51-like kinase 1 as a predictor of poor prognosis in colorectal cancer. Oncol. Lett. 2015;10:1583-1588.
Not in our library10.3892/ol.2015.3417
166.
Jiang S., Li Y., Zhu Y.H., Wu X.Q., Tang J., Li Z., Feng G.K., Deng R., Li D.D., Luo R.Z., et al. Intensive expression of UNC-51-like kinase 1 is a novel biomarker of poor prognosis in patients with esophageal squamous cell carcinoma. Cancer Sci. 2011;102:1568-1575.
Not in our library10.1111/j.1349-7006.2011.01964.x
167.
Dite T.A., Langendorf C.G., Hoque A., Galic S., Rebello R.J., Ovens A.J., Lindqvist L.M., Ngoei K.R.W., Ling N.X.Y., Furic L., et al. AMP-activated protein kinase selectively inhibited by the type II inhibitor SBI-0206965. J. Biol. Chem. 2018;293:8874-8885.
Not in our library10.1074/jbc.ra118.003547
168.
Lindmo K. Regulation of membrane traffic by phosphoinositide 3-kinases. J. Cell Sci. 2006;119:605-614.
Not in our library10.1242/jcs.02855
169.
Liu P., Cheng H., Roberts T.M., Zhao J.J. Targeting the phophoinositide 3-kinase(PI3K)pathway in cancer. Nat Rev Drug Discov. 2009;8:627-644.
Not in our library10.1038/nrd2926
170.
Leontieva O.V., Blagosklonny M. V Gerosuppression by pan-mTOR inhibitors. Aging (Albany. NY). 2016;8:3535-3551.
Not in our library10.18632/aging.101155
171.
Funderburk S.F., Wang Q.J., Yue Z. Public Access NIH Public Access. Trends Cell Biol. 2010;20:355-362.
Not in our library10.1016/j.tcb.2010.03.002
172.
Valet C., Levade M., Chicanne G., Bilanges B., Cabou C., Viaud J., Gratacap M.-P., Gaits-Iacovoni F., Vanhaesebroeck B., Payrastre B., et al. A dual role for the class III PI3K, Vps34, in platelet production and thrombus growth. Blood. 2017;130:2032-2042.
Not in our library10.1182/blood-2017-04-781641
173.
Tanida I., Sou Y.S., Ezaki J., Minematsu-Ikeguchi N., Ueno T., Kominami E. HsAtg4B/HsApg4B/autophagin-1 cleaves the carboxyl termini of three human Atg8 homologues and delipidates microtubule-associated protein light chain 3- and GABAA receptor-associated protein-phospholipid conjugates. J. Biol. Chem. 2004;279:36268-36276.
Not in our library10.1074/jbc.m401461200
174.
Yu Z.Q., Ni T., Hong B., Wang H.Y., Jiang F.J., Zou S., Chen Y., Zheng X.L., Klionsky D.J., Liang Y., et al. Dual roles of Atg8—PE deconjugation by Atg4 in autophagy. Autophagy. 2012;8:883-892.
Not in our library10.4161/auto.19652
175.
Fu Y., Huang Z., Hong L., Lu J.H., Feng D., Yin X.M., Li M. Targeting ATG4 in cancer therapy. Cancers. 2019;11:649.
Not in our library10.3390/cancers11050649
176.
Tran E., Chow A., Goda T., Wong A., Blakely K., Rocha M., Taeb S., Hoang V.C., Liu S.K., Emmenegger U. Context-dependent role of ATG4B as target for autophagy inhibition in prostate cancer therapy. Biochem. Biophys. Res. Commun. 2013;441:726-731.
Not in our library10.1016/j.bbrc.2013.10.117
177.
Bortnik S., Choutka C., Horlings H.M., Leung S., Baker J.H.E., Lebovitz C., Dragowska W.H., Go N.E., Bally M.B., Minchinton A.I., et al. Identification of breast cancer cell subtypes sensitive to ATG4B inhibition. Oncotarget. 2016;7.
Not in our library10.18632/oncotarget.11408
178.
Induction of Covalently Crosslinked p62 Oligomers with Reduced Binding to Polyubiquitinated Proteins by the Autophagy Inhibitor Verteporfin. · 2014
Not checked
179.
Zhang H., Ramakrishnan S.K., Triner D., Centofanti B., Maitra D., Győrffy B., Sebolt-Leopold J.S., Dame M.K., Varani J., Brenner D.E., et al. Tumor-selective proteotoxicity of verteporfin inhibits colon cancer progression independently of YAP1. Sci. Signal. 2015;8:ra98.
Not in our library10.1126/scisignal.aac5418
180.
Ota M., Sasaki H. Mammalian Tead proteins regulate cell proliferation and contact inhibition as transcriptional mediators of Hippo signaling. Development. 2008;135:4059-4069.
Not in our library10.1242/dev.027151
181.
Wei H., Wang F., Wang Y., Li T., Xiu P., Zhong J., Sun X., Li J. Verteporfin suppresses cell survival, angiogenesis and vasculogenic mimicry of pancreatic ductal adenocarcinoma via disrupting the YAP-TEAD complex. Cancer Sci. 2017;108:478-487.
Not in our library10.1111/cas.13138
182.
Melles R.B., Marmor M.F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA Ophthalmol. 2014;132:1453-1460.
Not in our library10.1001/jamaophthalmol.2014.3459
183.
Costedoat-Chalumeau N., Hulot J.-S., Amoura Z., Delcourt A., Maisonobe T., Dorent R., Bonnet N., Sablé R., Lechat P., Wechsler B., et al. Cardiomyopathy Related to Antimalarial Therapy with Illustrative Case Report. Cardiology. 2007;107:73-80.
Not in our library10.1159/000094079
184.
Marmor M.F., Kellner U., Lai T.Y.Y., Melles R.B., Mieler W.F., Lum F. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology. 2016;123:1386-1394.
Not in our library10.1016/j.ophtha.2016.01.058
185.
Bristol M.L., Emery S.M., Maycotte P., Thorburn A., Chakradeo S., Gewirtz D.A. Autophagy inhibition for chemosensitization and radiosensitization in cancer: Do the preclinical data support this therapeutic strategy? J. Pharmacol. Exp. Ther. 2013;344:544-552.
Not in our library10.1124/jpet.112.199802
186.
Bongiorno-Borbone L., Giacobbe A., Compagnone M., Eramo A., De Maria R., Peschiaroli A., Melino G. Anti-tumoral effect of desmethylclomipramine in lung cancer stem cells. Oncotarget. 2015;6:16926-16938.
Not in our library10.18632/oncotarget.4700
187.
Boya P., Casares N., Perfettini J., Dessen P., Larochette N., Métivier D., Meley D., Souquere S., Pierron G., Codogno P., et al. Inhibition of Macroautophagy Triggers Apoptosis. Mol. Cell. Biol. 2005;25:1025-1040.
Not in our library10.1128/mcb.25.3.1025-1040.2005
188.
Repurposing Drugs in Oncology (ReDO)—chloroquine and hydroxychloroquine as anti-cancer agents · 2017
No notice
189.
Piao S., Ojha R., Rebecca V.W., Samanta A., Ma X.H., Mcafee Q., Nicastri M.C., Buckley M., Brown E., Winkler J.D., et al. ALDH1A1 and HLTF modulate the activity of lysosomal autophagy inhibitors in cancer cells. Autophagy. 2017;13:2056-2071.
Not in our library10.1080/15548627.2017.1377377
190.
Maycotte P., Aryal S., Ct C., Thorburn J. Chloroquine sensitizes breast cancer cells to chemotherapy independent of autophagy. Autophagy. 2012;8:200-212.
Not in our library10.4161/auto.8.2.18554
191.
Eng C.H., Wang Z., Tkach D., Toral-Barza L., Ugwonali S., Liu S., Fitzgerald S.L., George E., Frias E., Cochran N., et al. Macroautophagy is dispensable for growth of KRAS mutant tumors and chloroquine efficacy. Proc. Natl. Acad. Sci. USA. 2016;113:182-187.
Not in our library10.1073/pnas.1515617113
192.
Degtyarev M., De Mazière A., Orr C., Lin J., Lee B.B., Tien J.Y., Prior W.W., Van Dijk S., Wu H., Gray D.C., et al. Akt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents. J. Cell Biol. 2008;183:101-116.
Not in our library10.1083/jcb.200801099
193.
Kwakye-Berko F., Meshnick S.R. Binding of chloroquine to DNA. Mol. Biochem. Parasitol. 1989;35:51-55.
Not in our library10.1016/0166-6851(89)90141-2
194.
Loehberg C.R., Strissel P.L., Dittrich R., Strick R., Dittmer J., Dittmer A., Fabry B., Kalender W.A., Koch T., Wachter D.L., et al. Akt and p53 are potential mediators of reduced mammary tumor growth by Chloroquine and the mTOR inhibitor RAD001. Biochem. Pharmacol. 2012;83:480-488.
Not in our library10.1016/j.bcp.2011.11.022
195.
Enzenmüller S., Gonzalez P., Debatin K.M., Fulda S. Chloroquine overcomes resistance of lung carcinoma cells to the dual PI3K/mTOR inhibitor PI103 by lysosome-mediated apoptosis. Anticancer. Drugs. 2013;24:14-19.
Not in our library10.1097/cad.0b013e32835a36db
196.
Kroemer G., Jäättelä M. Lysosomes and autophagy in cell death control. Nat. Rev. Cancer. 2005;5:886-897.
Not in our library10.1038/nrc1738
197.
Carew J.S., Nawrocki S.T., Kahue C.N., Zhang H., Yang C., Chung L., Houghton J.A., Huang P., Giles F.J., Cleveland J.L. Targeting autophagy augments the anticancer activity of the histone deacetylase inhibitor SAHAto overcome Bcr-Abl-mediated drug resistance. Blood. 2007;110:313-322.
Not in our library10.1182/blood-2006-10-050260
198.
Morgan M.J., Fitzwalter B.E., Owens C.R., Powers R.K., Sottnik J.L., Gamez G., Costello J.C., Theodorescu D., Thorburn A. Metastatic cells are preferentially vulnerable to lysosomal inhibition. Proc. Natl. Acad. Sci. USA. 2018;115:E8479-E8488.
Not in our library10.1073/pnas.1706526115
199.
Fennelly C., Amaravadi R.K. Lysosomal Biology in Cancer. Methods Mol Biol. 2017;1594:293-308.
Not in our library10.1007/978-1-4939-6934-0_19
200.
Uhlman A., Folkers K., Liston J., Pancholi H., Hinton A. Effects of Vacuolar H(+)-ATPase Inhibition on Activation of Cathepsin B and Cathepsin L Secreted from MDA-MB231 Breast Cancer Cells. Cancer Microenviron. 2017;10:49-56.
Not in our library10.1007/s12307-017-0196-7
201.
Balic A., Sørensen M.D., Trabulo S.M., Sainz B., Cioffi M., Vieira C.R., Miranda-Lorenzo I., Hidalgo M., Kleeff J., Erkan M., et al. Chloroquine Targets Pancreatic Cancer Stem Cells via Inhibition of CXCR4 and Hedgehog Signaling. Mol. Cancer Ther. 2014;13:1758-1771.
Not in our library10.1158/1535-7163.mct-13-0948
202.
Maes H., Kuchnio A., Peric A., Moens S., Nys K., DeBock K., Quaegebeur A., Schoors S., Georgiadou M., Wouters J., et al. Tumor vessel normalization by chloroquine independent of autophagy. Cancer Cell. 2014;26:190-206.
Not in our library10.1016/j.ccr.2014.06.025
203.
Mulcahy Levy J.M., Thompson J.C., Griesinger A.M., Amani V., Donson A.M., Birks D.K., Morgan M.J., Mirsky D.M., Handler M.H., Foreman N.K., et al. Autophagy Inhibition ImprovesChemosensitivity in BRAFV600E Brain Tumors. Cancer Discov. 2014;4:773-780.
Not in our library10.1158/2159-8290.cd-14-0049
204.
Kocaturk N.M., Akkoc Y., Kig C., Bayraktar O., Gozuacik D., Kutlu O. Autophagy as a molecular target for cancer treatment. Eur. J. Pharm. Sci. 2019;134:116-137.
Not in our library10.1016/j.ejps.2019.04.011
205.
Huang T., Kim C.K., Alvarez A.A., Pangeni R.P., Wan X., Song X., Shi T., Yang Y., Sastry N., Horbinski C.M., et al. MST4 Phosphorylation of ATG4B Regulates Autophagic Activity, Tumorigenicity, and Radioresistance in Glioblastoma. Cancer Cell. 2017;32:840-855.e8.
Not in our library10.1016/j.ccell.2017.11.005
206.
Chloroquine Enhances the Radiosensitivity of Bladder Cancer Cells by Inhibiting Autophagy and Activating Apoptosis · 2017
Not checked
207.
Daido S., Yamamoto A., Fujiwara K., Sawaya R., Kondo S., Kondo Y. Inhibition of the DNA-dependent protein kinase catalytic subunit radiosensitizes malignant glioma cells by inducing autophagy. Cancer Res. 2005;65:4368-4375.
Not in our library10.1158/0008-5472.can-04-4202
208.
Kim K.W., Hwang M., Moretti L., Jaboin J.J., Cha Y.I., Lu B. Autophagy upregulation by inhibitors of caspase-3 and mTOR enhances radiotherapy in a mouse model of lung cancer. Autophagy. 2008;4:659-668.
Not in our library10.4161/auto.6058
209.
Chiu H.W., Yeh Y.L., Wang Y.C., Huang W.J., Ho S.Y., Lin P., Wang Y.J. Combination of the novel histone deacetylase inhibitor YCW1 and radiation induces autophagic cell death through the downregulation of BNIP3 in triple-negative breast cancer cells in vitro and in an orthotopic mouse model. Mol. Cancer. 2016;15:1-12.
Not in our library10.1186/s12943-016-0531-5
210.
Scott K.A., Dalgleish A.G., Liu W.M. The combination of cannabidiol and Δ9-tetrahydrocannabinol enhances the anticancer effects of radiation in an orthotopic murine glioma model. Mol. Cancer Ther. 2014;13:2955-2967.
Not in our library10.1158/1535-7163.mct-14-0402
211.
Keshmiri-Neghab H., Goliaei B., Nikoofar A. Gossypol enhances radiation-induced autophagy in glioblastoma multiforme. Gen. Physiol. Biophys. 2014;33:433-442.
Not in our library10.4149/gpb_2014017
212.
Saleh T., Cuttino L., Gewirtz D.A. Autophagy is not uniformly cytoprotective: A personalized medicine approach for autophagy inhibition as a therapeutic strategy in non-small cell lung cancer. Biochim. Biophys. Acta. Gen. Subj. 2016;1860:2130-2136.
Not in our library10.1016/j.bbagen.2016.06.012
213.
Chakradeo S., Sharma K., Alhaddad A., Bakhshwin D., Le N., Harada H., Nakajima W., Yeudall W.A., Torti S.V., Torti F.M., et al. Yet another function of p53—The switch that determines whether radiation-induced autophagy will be cytoprotective or nonprotective: Implications for autophagy inhibition as a therapeutic strategy. Mol. Pharmacol. 2015;87:803-814.
Not in our library10.1124/mol.114.095273
214.
Singh K., Matsuyama S., Drazba J.A., Almasan A. Autophagy-dependent senescence in response to DNA damage and chronic apoptotic stress. Autophagy. 2012;8:236-251.
Not in our library10.4161/auto.8.2.18600
215.
Chen N., Wu L., Yuan H., Wang J. ROS/Autophagy/Nrf2 Pathway Mediated Low-Dose Radiation Induced Radio-Resistance in Human Lung Adenocarcinoma A549 Cell. Int. J. Biol. Sci. 2015;11:833-844.
Not in our library10.7150/ijbs.10564
216.
Kim E.J., Jeong J.H., Bae S., Kang S., Kim C.H., Lim Y. Bin MTOR inhibitors radiosensitize PTEN-deficient non-small-cell lung cancer cells harboring an EGFR activating mutation by inducing autophagy. J. Cell. Biochem. 2013;114:1248-1256.
Not in our library10.1002/jcb.24465
217.
Autophagy inhibition radiosensitizes in vitro, yet reduces radioresponses in vivo due to deficient immunogenic signalling · 2013
No notice
218.
The relationship between autophagy and the immune system and its applications for tumor immunotherapy · 2019
No notice
219.
Bhat P., Kriel J., Priya B.S., Shivananju N.S., Loos B. Modulating autophagy in cancer therapy: Advancements and challenges for cancer cell death sensitization. Biochem. Pharmacol. 2018;147:170-182.
Not in our library10.1016/j.bcp.2017.11.021
220.
Choi J.H., Yoon J.S., Won Y.W., Park B.B., Lee Y.Y. Chloroquine enhances the chemotherapeutic activity of 5-fluorouracil in a colon cancer cell line via cell cycle alteration. Apmis. 2012;120:597-604.
Not in our library10.1111/j.1600-0463.2012.02876.x
221.
Qin L., Xu T., Xia L., Wang X., Zhang X., Zhang X., Zhu Z., Zhong S., Wang C., Shen Z. Chloroquine enhances the efficacy of cisplatin by suppressing autophagy in human adrenocortical carcinoma treatment. Drug Des. Devel. Ther. 2016;10:1035-1045.
Not in our library10.2147/dddt.s101701
222.
Gonçalves R.M., Agnes J.P., Delgobo M., de Souza P.O., Thomé M.P., Heimfarth L., Lenz G., Moreira J.C.F., Zanotto-Filho A. Late autophagy inhibitor chloroquine improves efficacy of the histone deacetylase inhibitor SAHA and temozolomide in gliomas. Biochem. Pharmacol. 2019;163:440-450.
Not in our library10.1016/j.bcp.2019.03.015
223.
Hori Y.S., Hosoda R., Akiyama Y., Sebori R., Wanibuchi M., Mikami T., Sugino T., Suzuki K., Maruyama M., Tsukamoto M., et al. Chloroquine potentiates temozolomide cytotoxicity by inhibiting mitochondrial autophagy in glioma cells. J. Neurooncol. 2015;122:11-20.
Not in our library10.1007/s11060-014-1686-9
224.
Cufí S., Vazquez-Martin A., Oliveras-Ferraros C., Corominas-Faja B., Cuyàs E., López-Bonet E., Martin-Castillo B., Joven J., Menendez J.A. The anti-malarial chloroquine overcomes Primary resistance and restores sensitivity to Trastuzumab in HER2-positive breast cancer. Sci. Rep. 2013;3:1-13.
Not in our library10.1038/srep02469
225.
Scott A.J., Arcaroli J.J., Bagby S.M., Yahn R., Huber K.M., Serkova N.J., Nguyen A., Kim J., Thorburn A., Vogel J., et al. Cabozantinib Exhibits Potent Antitumor Activity in Colorectal Cancer Patient-Derived Tumor Xenograft Models via Autophagy and Signaling Mechanisms. Mol. Cancer Ther. 2018;17:2112-2122.
Not in our library10.1158/1535-7163.mct-17-0131
226.
Zhou P., Li Y., Li B., Zhang M., Xu C., Liu F., Bian L., Liu Y., Yao Y., Li D. Autophagy inhibition enhances celecoxib-induced apoptosis in osteosarcoma. Cell Cycle. 2018;17:997-1006.
Not in our library10.1080/15384101.2018.1467677
227.
Zhang X., Li W., Wang C., Leng X., Lian S., Feng J., Li J., Wang H. Inhibition of autophagy enhances apoptosis induced by proteasome inhibitor bortezomib in human glioblastoma U87 and U251 cells. Mol. Cell. Biochem. 2014;385:265-275.
Not in our library10.1007/s11010-013-1835-z
228.
Coordinate Autophagy and mTOR Pathway Inhibition Enhances Cell Death in Melanoma · 2013
No notice
229.
Kaneko M., Nozawa H., Hiyoshi M., Tada N., Murono K., Nirei T., Emoto S., Kishikawa J., Iida Y., Sunami E., et al. Temsirolimus and chloroquine cooperatively exhibit a potent antitumor effect against colorectal cancer cells. J. Cancer Res. Clin. Oncol. 2014;140:769-781.
Not in our library10.1007/s00432-014-1628-0
230.
Avniel-Polak S., Leibowitz G., Doviner V., Gross D.J., Grozinsky-Glasberg S. Combining Chloroquine with RAD001 Inhibits Tumor Growth in a NEN mouse model. Endocr. Relat. Cancer. 2018;25:677-686.
Not in our library10.1530/erc-18-0121
231.
Carew J.S., Medina E.C., Esquivel J.A., Mahalingam D., Swords R., Kelly K., Zhang H., Huang P., Mita A.C., Mita M.M., et al. Autophagy inhibition enhances vorinostat-induced apoptosis via ubiquitinated protein accumulation. J. Cell. Mol. Med. 2010;14:2448-2459.
Not in our library10.1111/j.1582-4934.2009.00832.x
232.
Pasquier B. SAR405, a PIK3C3/VPS34 inhibitor that prevents autophagy and synergizes with MTOR inhibition in tumor cells. Autophagy. 2015;11:725-726.
Not in our library10.1080/15548627.2015.1033601
233.
Pinto-Leite R., Arantes-Rodrigues R., Ferreira R., Palmeira C., Colaço A., Moreira da Silva V., Oliveira P., Lara Santos L. Temsirolimus improves cytotoxic efficacy of cisplatin and gemcitabine against urinary bladder cancer cell lines. Urol. Oncol. Semin. Orig. Investig. 2014;32:41.e11-41.e22.
Not in our library10.1016/j.urolonc.2013.04.012
234.
Wang H.W., Yang S.H., Huang G.D., Lin J.K., Chen W.S., Jiang J.K., Lan Y.T., Lin C.C., Hwang W.L., Tzeng C.H., et al. Temsirolimus enhances the efficacy of cetuximab in colon cancer through a CIP2A-dependent mechanism. J. Cancer Res. Clin. Oncol. 2014;140:561-571.
Not in our library10.1007/s00432-014-1596-4
235.
Curcumin overcome primary gefitinib resistance in non-small-cell lung cancer cells through inducing autophagy-related cell death · 2019
No notice
236.
Ma X.-H., Piao S.-F., Dey S., McAfee Q., Karakousis G., Villanueva J., Hart L.S., Levi S., Hu J., Zhang G., et al. Targeting ER stress-induced autophagy overcomes BRAF inhibitor resistance in melanoma. J. Clin. Investig. 2014;124:1406-1417.
Not in our library10.1172/jci70454
237.
Zhang H., Ren Y., Cao F., Chen J., Chen C., Chang J., Hou L., Zhang Z. In Situ Autophagy Disruption Generator for Cancer Theranostics. ACS Appl. Mater. Interfaces. 2019;11:29641-29654.
Not in our library10.1021/acsami.9b10578
238.
Wang Y., Shi K., Zhang L., Hu G., Wan J., Tang J., Yin S., Duan J., Qin M., Wang N., et al. Significantly enhanced tumor cellular and lysosomal hydroxychloroquine delivery by smart liposomes for optimal autophagy inhibition and improved antitumor efficiency with liposomal doxorubicin. Autophagy. 2016;12:949-962.
Not in our library10.1080/15548627.2016.1162930
239.
Wang X., Qiu Y., Yu Q., Li H., Chen X., Li M., Long Y., Liu Y., Lu L., Tang J., et al. Enhanced glioma therapy by synergistic inhibition of autophagy and tyrosine kinase activity. Int. J. Pharm. 2018;536:1-10.
Not in our library10.1016/j.ijpharm.2017.09.007
240.
Zhang X., Dong Y., Zeng X., Liang X., Li X., Tao W., Chen H., Jiang Y., Mei L., Feng S.-S. The effect of autophagy inhibitors on drug delivery using biodegradable polymer nanoparticles in cancer treatment. Biomaterials. 2014;35:1932-1943.
Not in our library10.1016/j.biomaterials.2013.10.034
241.
Zhang X., Yang Y., Liang X., Zeng X., Liu Z., Tao W., Xiao X., Chen H., Huang L., Mei L. Enhancing therapeutic effects of docetaxel-loaded dendritic copolymer nanoparticles by co-treatment with autophagy inhibitor on breast cancer. Theranostics. 2014;4:1085-1095.
Not in our library10.7150/thno.9933
242.
Feng Q., Yang X., Hao Y., Wang N., Feng X., Hou L., Zhang Z. Cancer Cell Membrane-Biomimetic Nanoplatform for Enhanced Sonodynamic Therapy on Breast Cancer via Autophagy Regulation Strategy. ACS Appl. Mater. Interfaces. 2019;11:32729-32738.
Not in our library10.1021/acsami.9b10948
243.
Zhou Z., Yan Y., Hu K., Zou Y., Li Y., Ma R., Zhang Q., Cheng Y. Autophagy inhibition enabled efficient photothermal therapy at a mild temperature. Biomaterials. 2017;141:116-124.
Not in our library10.1016/j.biomaterials.2017.06.030
244.
Ren X., Chen Y., Peng H., Fang X., Zhang X., Chen Q., Wang X., Yang W., Sha X. Blocking Autophagic Flux Enhances Iron Oxide Nanoparticle Photothermal Therapeutic Efficiency in Cancer Treatment. ACS Appl. Mater. Interfaces. 2018;10:27701-27711.
Not in our library10.1021/acsami.8b10167
245.
A chloroquine-induced macrophage-preconditioning strategy for improved nanodelivery · 2017
No notice
246.
Lv T., Li Z., Xu L., Zhang Y., Chen H., Gao Y. Chloroquine in combination with aptamer-modified nanocomplexes for tumor vessel normalization and efficient erlotinib/Survivin shRNA co-delivery to overcome drug resistance in EGFR-mutated non-small cell lung cancer. Acta Biomater. 2018;76:257-274.
Not in our library10.1016/j.actbio.2018.06.034
247.
Wang P., Burikhanov R., Jayswal R., Weiss H.L., Arnold S.M., Villano J.L., Rangnekar V.M. Neoadjuvant administration of hydroxychloroquine in a phase 1 clinical trial induced plasma Par-4 levels and apoptosis in diverse tumors. Genes Cancer. 2018;9:190-197.
Not in our library10.18632/genesandcancer.181
248.
Wolpin B.M., Rubinson D.A., Wang X., Chan J.A., Cleary J.M., Enzinger P.C., Fuchs C.S., McCleary N.J., Meyerhardt J.A., Ng K., et al. Phase II and pharmacodynamic study of autophagy inhibition using hydroxychloroquine in patients with metastatic pancreatic adenocarcinoma. Oncologist. 2014;19:637-638.
Not in our library10.1634/theoncologist.2014-0086
249.
Goldberg S.B., Supko J.G., Neal J.W., Muzikansky A., Digumarthy S., Fidias P., Temel J.S., Heist R.S., Shaw A.T., McCarthy P.O., et al. A phase I study of erlotinib and hydroxychloroquine in advanced non-small-cell lung cancer. J. Thorac. Oncol. 2012;7:1602-1608.
Not in our library10.1097/jto.0b013e318262de4a
250.
Rangwala R., Leone R., Chang Y.C., Fecher L.A., Schuchter L.M., Kramer A., Tan K.S., Heitjan D.F., Rodgers G., Gallagher M., et al. Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma. Autophagy. 2014;10:1369-1379.
Not in our library10.4161/auto.29118
251.
Vogl D.T., Stadtmauer E.A., Tan K.S., Heitjan D.F., Davis L.E., Pontiggia L., Rangwala R., Piao S., Chang Y.C., Scott E.C., et al. Combined autophagy and proteasome inhibition a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma. Autophagy. 2014;10:1380-1390.
Not in our library10.4161/auto.29264
252.
Rosenfeld M.R., Ye X., Supko J.G., Desideri S., Grossman S.A., Brem S., Mikkelson T., Wang D., Chang Y.C., Hu J., et al. A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme. Autophagy. 2014;10:1359-1368.
Not in our library10.4161/auto.28984
253.
Sotelo J., Briceño E., López-González M.A. Adding chloroquine to conventional treatment for glioblastoma multiforme: A randomized, double-blind, placebo-controlled trial. Ann. Intern. Med. 2006;144:337-343.
Not in our library10.7326/0003-4819-144-5-200603070-00008
254.
Briceño E., Reyes S., Sotelo J. Therapy of glioblastoma multiforme improved by the antimutagenic chloroquine. Neurosurg. Focus. 2003;14:2-7.
Not in our library10.3171/foc.2003.14.2.4
255.
Rojas-Puentes L.L., Gonzalez-Pinedo M., Crismatt A., Ortega-Gomez A., Gamboa-Vignolle C., Nuñez-Gomez R., Dorantes-Gallareta Y., Arce-Salinas C., Arrieta O. Phase II randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases. Radiat. Oncol. 2013;8.
Not in our library10.1186/1748-717x-8-209
256.
Autophagy inhibition overcomes multiple mechanisms of resistance to BRAF inhibition in brain tumors · 2017
No notice
257.
Schelman W.R., Mohammed T.A., Traynor A.M., Kolesar J.M., Marnocha R.M., Eickhoff J., Keppen M., Alberti D.B., Wilding G., Takebe N., et al. A phase I study of AT-101 with cisplatin and etoposide in patients with advanced solid tumors with an expanded cohort in extensive-stage small cell lung cancer. Investig. New Drugs. 2014;32:295-302.
Not in our library10.1007/s10637-013-9999-7
258.
Swiecicki P.L., Bellile E., Sacco A.G., Pearson A.T., Taylor J.M.G., Jackson T.L., Chepeha D.B., Spector M.E., Shuman A., Malloy K., et al. A phase II trial of the BCL-2 homolog domain 3 mimetic AT-101 in combination with docetaxel for recurrent, locally advanced, or metastatic head and neck cancer. Investig. New Drugs. 2016;34:481-489.
Not in our library10.1007/s10637-016-0364-5
259.
Stein M.N., Hussain M., Stadler W.M., Liu G., Tereshchenko I.V., Goodin S., Jeyamohan C., Kaufman H.L., Mehnert J., Dipaola R.S. A Phase II Study of AT-101 to Overcome Bcl-2-Mediated Resistance to Androgen Deprivation Therapy in Patients with Newly Diagnosed Castration-Sensitive Metastatic Prostate Cancer. Clin. Genitourin. Cancer. 2016;14:22-27.
Not in our library10.1016/j.clgc.2015.09.010
260.
A phase II study of the histone deacetylase inhibitor vorinostat combined with tamoxifen for the treatment of patients with hormone therapy-resistant breast cancer · 2011
No notice
261.
Mahalingam D., Mita M., Sarantopoulos J., Wood L., Amaravadi R.K., Davis L.E., Mita A.C., Curiel T.J., Espitia C.M., Nawrocki S.T., et al. Combined autophagy and HDAC inhibition: A phase I safety, tolerability, pharmacokinetic, and pharmacodynamic analysis of hydroxychloroquine in combination with the HDAC inhibitor vorinostat in patients with advanced solid tumors. Autophagy. 2014;10:1403-1414.
Not in our library10.4161/auto.29231
262.
Margolin K., Longmate J., Baratta T., Synold T., Christensen S., Weber J., Gajewski T., Quirt I., Doroshow J.H. CCI-779 in metastatic melanoma: A phase II trial of the California Cancer Consortium. Cancer. 2005;104:1045-1048.
Not in our library10.1002/cncr.21265
263.
El-Chemaly S., Taveira-Dasilva A., Goldberg H.J., Peters E., Haughey M., Bienfang D., Jones A.M., Julien-Williams P., Cui Y., Villalba J.A., et al. Sirolimus and Autophagy Inhibition in Lymphangioleiomyomatosis: Results of a Phase I Clinical Trial. Chest. 2017;151:1302-1310.
Not in our library10.1016/j.chest.2017.01.033
264.
Chi K.H., Ko H.L., Yang K.L., Lee C.Y., Chi M.S., Kao S.J. Addition of rapamycin and hydroxychloroquine to metronomic chemotherapy as a second line treatment results in high salvage rates for refractory metastatic solid tumors: A pilot safety and effectiveness analysis in a small patient cohort. Oncotarget. 2015;6:16735-16745.
Not in our library10.18632/oncotarget.3793
265.
Rangwala R., Chang Y.C., Hu J., Algazy K.M., Evans T.L., Fecher L.A., Schuchter L.M., Torigian D.A., Panosian J.T., Troxel A.B., et al. Combined MTOR and autophagy inhibition: Phase I trial of hydroxychloroquine and temsirolimus in patients with advanced solid tumors and melanoma. Autophagy. 2014;10:1391-1402.
Not in our library10.4161/auto.29119
266.
Chloroquine reduces hypercoagulability in pancreatic cancer through inhibition of neutrophil extracellular traps · 2018
No notice
267.
Miller-Ocuin J.L., Liang X., Boone B.A., Doerfler W.R., Singhi A.D., Tang D., Kang R., Lotze M.T., Zeh H.J. DNA released from neutrophil extracellular traps (NETs) activates pancreatic stellate cells and enhances pancreatic tumor growth. Oncoimmunology. 2019;8:e1605822.
Not in our library10.1080/2162402x.2019.1605822
268.
Boone B.A., Bahary N., Zureikat A.H., Moser A.J., Normolle D.P., Wu W.C., Singhi A.D., Bao P., Bartlett D.L., Liotta L.A., et al. Safety and Biologic Response of Pre-operative Autophagy Inhibition in Combination with Gemcitabine in Patients with Pancreatic Adenocarcinoma. Ann. Surg. Oncol. 2015;22:4402-4410.
Not in our library10.1245/s10434-015-4566-4
269.
Chi M.-S., Lee C.-Y., Huang S.-C., Yang K.-L., Ko H.-L., Chen Y.-K., Chung C.-H., Liao K.-W., Chi K.-H. Double autophagy modulators reduce 2-deoxyglucose uptake in sarcoma patients. Oncotarget. 2015;6:29808-29817.
Not in our library10.18632/oncotarget.5060
270.
Tang Y., El-Chemaly S., Taveira-Dasilva A., Goldberg H.J., Bagwe S., Rosas I.O., Moss J., Priolo C., Henske E.P. Metabolic Changes in Patients With Lymphangioleiomyomatosis Treated With Sirolimus and Hydroxychloroquine. Chest. 2019.
Not in our library10.1016/j.chest.2019.05.038
271.
Lamattina A.M., Taveira-Dasilva A., Goldberg H.J., Bagwe S., Cui Y., Rosas I.O., Moss J., Henske E.P., El-Chemaly S. Circulating Biomarkers From the Phase 1 Trial of Sirolimus and Autophagy Inhibition for Patients With Lymphangioleiomyomatosis. Chest. 2018;154:1070-1082.
Not in our library10.1016/j.chest.2018.08.1029
272.
Bilger A., Bittner M.-I., Grosu A.-L., Wiedenmann N., Meyer P.T., Firat E., Niedermann G., Weber W.A., Milanović D. FET-PET-based reirradiation and chloroquine in patients with recurrent glioblastomaFET-PET-basierte Rebestrahlung und Chloroquin bei Patienten mit rezidiviertem Glioblastom. Strahlentherapie und Onkol. 2014;190:957-961.
Not in our library10.1007/s00066-014-0693-2
273.
Eldredge H.B., DeNittis A., DuHadaway J.B., Chernick M., Metz R., Prendergast G.C. Concurrent whole brain radiotherapy and short-course chloroquine in patients with brain metastases: A pilot trial. J. Radiat. Oncol. 2013;2:315-321.
Not in our library10.1007/s13566-013-0111-x

Cited by papers we hold 2

SCD1, autophagy and cancer: implications for therapy · 2021
No notice
The Double-Edge Sword of Autophagy in Cancer: From Tumor Suppression to Pro-tumor Activity · 2020
No notice

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