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Retinoids: present role and future potential

T R J Evans, S B Kaye

British Journal of Cancer · 1999 · Review

doi:10.1038/sj.bjc.6690312

Abstract

Vitamin A and its biologically active derivatives, retinal and retinoic acid (RA), together with a large repertoire of synthetic analogues are collectively referred to as retinoids. Naturally occurring retinoids regulate the growth and differentiation of a wide variety of cell types and play a crucial role in the physiology of vision and as morphogenic agents during embryonic development. Retinoids and their analogues have been evaluated as chemoprevention agents, and also in the management of acute promyelocytic leukaemia. Retinoids exert most of their effects by binding to specific receptors and modulating gene expression. The development of new active retinoids and the identification of two distinct families of retinoid receptors has led to an increased understanding of the cellular effects of activation of these receptors. In this article we review the use of retinoids in chemoprevention strategies, discuss the cellular consequences of activated retinoid receptors, and speculate on how our increasing understanding of retinoid-induced signalling pathways may contribute to future therapeutic strategies in the management of malignant disease.

References 125

  1. 1.

    Allenby G., Bocquel M. T., Saunders M., Kazmer S., Speck J., Rosenberger M., Lovey A., Kastner P., Grippo J. F., Chambon P. Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids. Proc Natl Acad Sci U S A. 1993;90(1):30-34.

    Not in our library10.1073/pnas.90.1.30

  2. 2.

    Anzano M. A., Byers S. W., Smith J. M., Peer C. W., Mullen L. T., Brown C. C., Roberts A. B., Sporn M. B. Prevention of breast cancer in the rat with 9-cis-retinoic acid as a single agent and in combination with tamoxifen. Cancer Res. 1994;54(17):4614-4617.

    Not in our library

  3. 3.

    Arnold A., Ayoub J., Douglas L., Hoogendoorn P., Skingley L., Gelmon K., Hirsh V., Eisenhauer E. Phase II trial of 13-cis-retinoic acid plus interferon alpha in non-small-cell lung cancer. The National Cancer Institute of Canada Clinical Trials Group. J Natl Cancer Inst. 1994;86(4):306-309.

    Not in our library10.1093/jnci/86.4.306

  4. 4.

    Atencia R., García-Sanz M., Unda F., Aréchaga J. Apoptosis during retinoic acid-induced differentiation of F9 embryonal carcinoma cells. Exp Cell Res. 1994;214(2):663-667.

    Not in our library10.1006/excr.1994.1304

  5. 5.

    Bavinck J. N., Tieben L. M., Van der Woude F. J., Tegzess A. M., Hermans J., ter Schegget J., Vermeer B. J. Prevention of skin cancer and reduction of keratotic skin lesions during acitretin therapy in renal transplant recipients: a double-blind, placebo-controlled study. J Clin Oncol. 1995;13(8):1933-1938.

    Not in our library10.1200/jco.1995.13.8.1933

  6. 6.

    Benner S. E., Pajak T. F., Lippman S. M., Earley C., Hong W. K. Prevention of second primary tumors with isotretinoin in patients with squamous cell carcinoma of the head and neck: long-term follow-up. J Natl Cancer Inst. 1994;86(2):140-141.

    Not in our library10.1093/jnci/86.2.140

  7. 7.

    Bolla M., Lefur R., Ton Van J., Domenge C., Badet J. M., Koskas Y., Laplanche A. Prevention of second primary tumours with etretinate in squamous cell carcinoma of the oral cavity and oropharynx. Results of a multicentric double-blind randomised study. Eur J Cancer. 1994;30A(6):767-772.

    Not in our library10.1016/0959-8049(94)90290-9

  8. 8.

    Bollag W., Majewski S., Jablonska S. Cancer combination chemotherapy with retinoids: experimental rationale. Leukemia. 1994;8(Suppl 3):S11-S15.

    Not in our library

  9. 9.

    Caliaro M. J., Vitaux P., Lafon C., Lochon I., Néhmé A., Valette A., Canal P., Bugat R., Jozan S. Multifactorial mechanism for the potentiation of cisplatin (CDDP) cytotoxicity by all-trans retinoic acid (ATRA) in human ovarian carcinoma cell lines. Br J Cancer. 1997;75(3):333-340.

    Not in our library10.1038/bjc.1997.55

  10. 10.

    Castaigne S., Chomienne C., Daniel M. T., Ballerini P., Berger R., Fenaux P., Degos L. All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results. Blood. 1990;76(9):1704-1709.

    Not in our library

  11. 11.

    Chambon P. The molecular and genetic dissection of the retinoid signaling pathway. Recent Prog Horm Res. 1995;50:317-332.

    Not in our library10.1016/b978-0-12-571150-0.50019-6

  12. 12.

    Chen J. D., Evans R. M. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature. 1995;377(6548):454-457.

    Not in our library10.1038/377454a0

  13. 13.

    Chen J. Y., Clifford J., Zusi C., Starrett J., Tortolani D., Ostrowski J., Reczek P. R., Chambon P., Gronemeyer H. Two distinct actions of retinoid-receptor ligands. Nature. 1996;382(6594):819-822.

    Not in our library10.1038/382819a0

  14. 14.

    Chen Z. X., Xue Y. Q., Zhang R., Tao R. F., Xia X. M., Li C., Wang W., Zu W. Y., Yao X. Z., Ling B. J. A clinical and experimental study on all-trans retinoic acid-treated acute promyelocytic leukemia patients. Blood. 1991;78(6):1413-1419.

    Not in our library

  15. 15.

    Chiesa F., Tradati N., Marazza M., Rossi N., Boracchi P., Mariani L., Formelli F., Giardini R., Costa A., De Palo G. Fenretinide (4-HPR) in chemoprevention of oral leukoplakia. J Cell Biochem Suppl. 1993;17F:255-261.

    Not in our library10.1002/jcb.240531038

  16. 16.

    Colston K. W., Mackay A. G., James S. Y., Binderup L., Chander S., Coombes R. C. EB1089: a new vitamin D analogue that inhibits the growth of breast cancer cells in vivo and in vitro. Biochem Pharmacol. 1992;44(12):2273-2280.

    Not in our library10.1016/0006-2952(92)90669-a

  17. 17.

    Costa A., De Palo G., Decensi A., Formelli F., Chiesa F., Nava M., Camerini T., Marubini E., Veronesi U. Retinoids in cancer chemoprevention. Clinical trials with the synthetic analogue fenretinide. Ann N Y Acad Sci. 1995;768:148-162.

    Not in our library10.1111/j.1749-6632.1995.tb12118.x

  18. 18.

    Costa A., Formelli F., Chiesa F., Decensi A., De Palo G., Veronesi U. Prospects of chemoprevention of human cancers with the synthetic retinoid fenretinide. Cancer Res. 1994;54(7 Suppl):2032s-2037s.

    Not in our library

  19. 19.

    Creek K. E., Jenkins G. R., Khan M. A., Batova A., Hodam J. R., Tolleson W. H., Pirisi L. Retinoic acid suppresses human papillomavirus type 16 (HPV16)-mediated transformation of human keratinocytes and inhibits the expression of the HPV16 oncogenes. Adv Exp Med Biol. 1994;354:19-35.

    Not in our library10.1007/978-1-4899-0939-8_2

  20. 20.

    Darwiche N., Scita G., Jones C., Rutberg S., Greenwald E., Tennenbaum T., Collins S. J., De Luca L. M., Yuspa S. H. Loss of retinoic acid receptors in mouse skin and skin tumors is associated with activation of the ras(Ha) oncogene and high risk for premalignant progression. Cancer Res. 1996;56(21):4942-4949.

    Not in our library

  21. 21.

    Dey A., Minucci S., Ozato K. Ligand-dependent occupancy of the retinoic acid receptor beta 2 promoter in vivo. Mol Cell Biol. 1994;14(12):8191-8201.

    Not in our library10.1128/mcb.14.12.8191-8201.1994

  22. 22.

    Dhingra K., Papadopoulos N., Lippman S., Lotan R., Legha S. S. Phase II study of alpha-interferon and 13-cis-retinoic acid in metastatic melanoma. Invest New Drugs. 1993;11(1):39-43.

    Not in our library10.1007/bf00873908

  23. 23.

    Durand B., Saunders M., Leroy P., Leid M., Chambon P. All-trans and 9-cis retinoic acid induction of CRABPII transcription is mediated by RAR-RXR heterodimers bound to DR1 and DR2 repeated motifs. Cell. 1992;71(1):73-85.

    Not in our library10.1016/0092-8674(92)90267-g

  24. 24.

    Edwards L., Jaffe P. The effect of topical tretinoin on dysplastic nevi. A preliminary trial. Arch Dermatol. 1990;126(4):494-499.

    Not in our library

  25. 25.

    Eisenhauer E. A., Lippman S. M., Kavanagh J. J., Parades-Espinoza M., Arnold A., Hong W. K., Massimini G., Schleuniger U., Bollag W., Holdener E. E. Combination 13-cis-retinoic acid and interferon alpha-2a in the therapy of solid tumors. Leukemia. 1994;8(Suppl 3):S38-S41.

    Not in our library

  26. 26.

    Elstner E., Linker-Israeli M., Umiel T., Le J., Grillier I., Said J., Shintaku I. P., Krajewski S., Reed J. C., Binderup L. Combination of a potent 20-epi-vitamin D3 analogue (KH 1060) with 9-cis-retinoic acid irreversibly inhibits clonal growth, decreases bcl-2 expression, and induces apoptosis in HL-60 leukemic cells. Cancer Res. 1996;56(15):3570-3576.

    Not in our library

  27. 27.

    Evans R. M., Hollenberg S. M. Zinc fingers: gilt by association. Cell. 1988;52(1):1-3.

    Not in our library10.1016/0092-8674(88)90522-3

  28. 28.

    Evans R. M. The steroid and thyroid hormone receptor superfamily. Science. 1988;240(4854):889-895.

    Not in our library10.1126/science.3283939

  29. 29.

    Fan S., el-Deiry W. S., Bae I., Freeman J., Jondle D., Bhatia K., Fornace A. J., Magrath I., Kohn K. W., O'Connor P. M. p53 gene mutations are associated with decreased sensitivity of human lymphoma cells to DNA damaging agents. Cancer Res. 1994;54(22):5824-5830.

    Not in our library

  30. 30.

    Fanjul A. N., Bouterfa H., Dawson M., Pfahl M. Potential role for retinoic acid receptor-gamma in the inhibition of breast cancer cells by selective retinoids and interferons. Cancer Res. 1996;56(7):1571-1577.

    Not in our library

  31. 31.

    Fenaux P., Castaigne S., Dombret H., Archimbaud E., Duarte M., Morel P., Lamy T., Tilly H., Guerci A., Maloisel F. All-transretinoic acid followed by intensive chemotherapy gives a high complete remission rate and may prolong remissions in newly diagnosed acute promyelocytic leukemia: a pilot study on 26 cases. Blood. 1992;80(9):2176-2181.

    Not in our library

  32. 32.

    Fontana J. A. Interaction of retinoids and tamoxifen on the inhibition of human mammary carcinoma cell proliferation. Exp Cell Biol. 1987;55(3):136-144.

    Not in our library10.1159/000163409

  33. 33.

    Fontana J. A., Miranda D., Mezu A. B. Retinoic acid inhibition of human breast carcinoma proliferation is accompanied by inhibition of the synthesis of a Mr 39,000 protein. Cancer Res. 1990;50(7):1977-1982.

    Not in our library

  34. 34.

    Frankel S. R., Eardley A., Heller G., Berman E., Miller W. H., Dmitrovsky E., Warrell R. P. All-trans retinoic acid for acute promyelocytic leukemia. Results of the New York Study. Ann Intern Med. 1994;120(4):278-286.

    Not in our library10.7326/0003-4819-120-4-199402150-00004

  35. 35.

    Freedman L. P. Anatomy of the steroid receptor zinc finger region. Endocr Rev. 1992;13(2):129-145.

    Not in our library10.1210/edrv-13-2-129

  36. 36.

    Gianni M., Terao M., Fortino I., LiCalzi M., Viggiano V., Barbui T., Rambaldi A., Garattini E. Stat1 is induced and activated by all-trans retinoic acid in acute promyelocytic leukemia cells. Blood. 1997;89(3):1001-1012.

    Not in our library

  37. 37.

    Giguere V., Ong E. S., Segui P., Evans R. M. Identification of a receptor for the morphogen retinoic acid. Nature. 1987;330(6149):624-629.

    Not in our library10.1038/330624a0

  38. 38.

    Giguère V. Retinoic acid receptors and cellular retinoid binding proteins: complex interplay in retinoid signaling. Endocr Rev. 1994;15(1):61-79.

    Not in our library10.1210/edrv-15-1-61

  39. 39.

    Gorry P., Lufkin T., Dierich A., Rochette-Egly C., Décimo D., Dollé P., Mark M., Durand B., Chambon P. The cellular retinoic acid binding protein I is dispensable. Proc Natl Acad Sci U S A. 1994;91(19):9032-9036.

    Not in our library10.1073/pnas.91.19.9032

  40. 40.

    Gottardis M. M., Bischoff E. D., Shirley M. A., Wagoner M. A., Lamph W. W., Heyman R. A. Chemoprevention of mammary carcinoma by LGD1069 (Targretin): an RXR-selective ligand. Cancer Res. 1996;56(24):5566-5570.

    Not in our library

All 125 references

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