Tropomyosin receptor kinase (TRK) biology and the role of NTRK gene fusions in cancer

Abstract

The tropomyosin receptor kinase (TRK) family of receptor tyrosine kinases are encoded by NTRK genes and have a role in the development and normal functioning of the nervous system. Since the discovery of an oncogenic NTRK gene fusion in colorectal cancer in 1986, over 80 different fusion partner genes have been identified in a wide array of adult and paediatric tumours, providing actionable targets for targeted therapy. This review describes the normal function and physiology of TRK receptors and the biology behind NTRK gene fusions and how they act as oncogenic drivers in cancer. Finally, an overview of the incidence and prevalence of NTRK gene fusions in various types of cancers is discussed.

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     No notice
105. 105.

     Pishvaian MJ, Rolfo CD, Liu SV et al Clinical benefit of entrectinib for patients with metastatic pancreatic cancer who harbor NTRK and ROS1 fusions. J Clin Oncol2018; 36(Suppl 4): 521.

     Not in our library

106. 106.

     Andreasen S, Skalova A, Agaimy A et al ETV6 gene rearrangements characterize a morphologically distinct subset of sinonasal low-grade non-intestinal-type adenocarcinoma: a novel translocation-associated carcinoma restricted to the sinonasal tract. Am J Surg Pathol2017; 41(11): 1552–1560.

     Not in our library10.1097/pas.0000000000000912

107. 107.

     Sigal D, Tartar M, Xavier M et al Activity of entrectinib in a patient with the first reported NTRK fusion in neuroendocrine cancer. J Natl Compr Canc Netw2017; 15(11): 1317–1322.

     Not in our library10.6004/jnccn.2017.7029

108. 108.

     Roberts KG, Li Y, Payne-Turner D et al Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med2014; 371(11): 1005–1015.

     Not in our library10.1056/nejmoa1403088

109. 109.

     Eguchi M, Eguchi-Ishimae M, Tojo A et al Fusion of ETV6 to neurotrophin-3 receptor TRKC in acute myeloid leukemia with t(12; 15)(p13; q25). Blood1999; 93(4): 1355–1363.

     Not in our library

110. 110.

     Cook PJ, Thomas R, Kannan R et al Somatic chromosomal engineering identifies BCAN-NTRK1 as a potent glioma driver and therapeutic target. Nat Commun2017; 8(1): 15987.

     Not in our library10.1038/ncomms15987

111. 111.

     Medico E, Russo M, Picco G et al The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets. Nat Commun2015; 6(1): 7002.

     Not in our library10.1038/ncomms8002

112. 112.

     Li Z, Tognon CE, Godinho FJ et al ETV6-NTRK3 fusion oncogene initiates breast cancer from committed mammary progenitors via activation of AP1 complex. Cancer Cell2007; 12(6): 542–558.

     Not in our library10.1016/j.ccr.2007.11.012

113. 113.

     Lee SJ, Li GG, Kim ST et al NTRK1 rearrangement in colorectal cancer patients: evidence for actionable target using patient-derived tumor cell line. Oncotarget2015; 6(36): 39028–39035.

     Not in our library10.18632/oncotarget.5494

114. 114.

     Drilon A, Nagasubramanian R, Blake JF et al A next-generation TRK kinase inhibitor overcomes acquired resistance to prior TRK kinase inhibition in patients with TRK fusion-positive solid tumors. Cancer Discov2017; 7(9): 963–972.

     Not in our library10.1158/2159-8290.cd-17-0507

115. 115.

     Demetri GD, Paz-Ares L, Farago AF et al Efficacy and safety of entrectinib in patients with NTRK fusion-positive (NTRK-fp) tumors: pooled analysis of STARTRK-2, STARTRK-1 and ALKA-372-001. In ESMO 2018 Congress, Munich, Germany, LBA17, 2018.

     Not in our library

116. 116.

     Lassen UN, Albert CM, Kummar S et al Larotrectinib efficacy and safety in TRK fusion cancer: an expanded clinical dataset showing consistency in an age and tumor agnostic approach. Ann Oncol2018; 29(Suppl 8): viii133–viii148.

     Not in our library

117. 117.

     Hong DS, Bauer TM, Lee JJ et al Larotrectinib in adult patients with solid tumours: a multi-centre, open-label, phase I dose-escalation study. Ann Oncol2019; 30(2): 325–331.

     Not in our library10.1093/annonc/mdy539

118. 118.

     Russo M, Misale S, Wei G et al Acquired resistance to the TRK inhibitor entrectinib in colorectal cancer. Cancer Discov2016; 6(1): 36–44.

     Not in our library10.1158/2159-8290.cd-15-0940

119. 119.

     Okamura R, Boichard A, Kato S et al Analysis of NTRK alterations in pan-cancer adult and pediatric malignancies: implications for NTRK-targeted therapeutics. JCO Precis Oncol2018; 2(1): 1.

     Not in our library10.1200/po.18.00183

120. 120.

     Nanda N, Fennell T, Low JA. Identification of tropomyosin kinase receptor (TRK) mutations in cancer. J Clin Oncol2015; 33(Suppl 15): 1553.

     Not in our library

Cited by papers we hold 4

• Small molecule inhibitors targeting the cancers · 2022
  No notice
• Circulating tumor DNA to guide rechallenge with panitumumab in metastatic colorectal cancer: the phase 2 CHRONOS trial · 2022
  No notice
• Applicability of pan-TRK immunohistochemistry for identification of NTRK fusions in lung carcinoma · 2021
  Not checked
• Diagnosis and management of tropomyosin receptor kinase (TRK) fusion sarcomas: expert recommendations from the World Sarcoma Network · 2020
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.