Abstract
Retinoids are natural and synthetic derivatives of vitamin A. The anticancer properties of retinoids have been extensively investigated in the preclinical, epidemiological and clinical settings. The primary targets of the retinoids are retinoid receptors. Retinoid receptors are ligand-activated transcription factors, members of the steroid nuclear receptor family. Retinoid receptors are deregulated in a number of malignant diseases including the fusion of RARĪ± with PML in acute promyelocytic leukemia (APL) and the repression of RARĪ² in lung and head and neck cancers. In some cases, pharmacologic doses of retinoids can overcome these cancer specific defects in retinoid signaling. High-doses of retinoids induce differentiation and apoptosis of tumor cells, which is related to their physiologic effects in regulating embryonic development and maturation during hematopoiesis and in diverse epithelial tissues. Retinoid receptors have been cancer therapy targets for more than 30 years, and there are a number of FDA-approved retinoid-based therapies, the most impactful is the standard of care of all-trans-retinoic acid induced differentiation therapy of APL. Clinical evaluation of retinoids, especially newer synthetic retinoids in combination with molecular targeted and epigenetic therapy remains an active area of investigation in oncology.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Dezube BJ, Pantanowitz L, Aboulafia DM. Management of AIDS-related Kaposi sarcoma: advances in target discovery and treatment. AIDS Read. 2004;14:236ā8.
Dragnev KH, Petty WJ, Shah S, Biddle A, Desai NB, Memoli V, Rigas JR, Dmitrovsky E. Bexarotene and erlotinib for aerodigestive tract cancer. J Clin Oncol. 2005;23:8757ā64.
Dragnev KH, Petty WJ, Shah SJ, Lewis LD, Black CC, Memoli V, Nugent WC, Hermann T, Negro-Vilar A, Rigas JR, Dmitrovsky E. A proof-of-principle clinical trial of bexarotene in patients with non-small cell lung cancer. Clin Cancer Res. 2007;13:1794ā800.
Duester G. Retinoic acid synthesis and signaling during early organogenesis. Cell. 2008;134:921ā31.
Freemantle SJ, Spinella MJ, Dmitrovsky E. Retinoids in cancer therapy and chemoprevention: promise meets resistance. Oncogene. 2003;22:7305ā15.
Freemantle SJ, Liu X, Feng Q, Galimberti F, Blumen S, Sekula D, Kitareewan S, Dragnev KH, Dmitrovsky E. Cyclin degradation for cancer therapy and chemoprevention. J Cell Biochem. 2007;102:869ā77.
Germain P, Chambon P, Eichele G, Evans RM, Lazar MA, Leid M, De Lera AR, Lotan R, Mangelsdorf DJ, Gronemeyer H. International Union of Pharmacology. LX. Retinoic acid receptors. Pharmacol Rev. 2006a;58:712ā25.
Germain P, Chambon P, Eichele G, Evans RM, Lazar MA, Leid M, De Lera AR, Lotan R, Mangelsdorf DJ, Gronemeyer H. International Union of Pharmacology. LXIII. Retinoic X receptors. Pharmacol Rev. 2006b;58:760ā72.
Goodman GE, Thornquist MD, Balmes J, Cullen MR, Meyskens Jr FL, Omenn GS, Valanis B, Williams Jr JH. The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements. J Natl Cancer Inst. 2004;96:1743ā50.
Grimwade D, Mistry AR, Solomon E, Guidez F. Acute promyelocytic leukemia: a paradigm for differentiation therapy. Cancer Treat Res. 2010;145:219ā35.
Klass CM, Shin DM. Current status and further development of chemoprevention in head and neck cancer. Curr Cancer Drug Targets. 2007;7:623ā32.
Lansigan F, Foss FM. Current and emerging treatment strategies for cutaneous T-cell lymphoma. Drugs. 2010;70:273ā86.
Lippman SM, Lotan R. Advances in the development of retinoids as chemoprevention agents. J Nutr. 2000;130:479Sā82.
Lippman SM, Heyman RA, Kurie JM, Benner SE, Hong WK. Retinoids and chemoprevention: clinical and basic studies. J Cell Biochem Suppl. 1995;22:1ā10.
Matthay KM, Reynolds CP, Seeger RC, Shimada H, Adkins ES, Haas-Kogan D, Gerbing RB, London WB, Villablanca JG. Long-term results from children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a Childrenās Oncology Group study. J Clin Oncol. 2009;27:1007ā13.
Moon RC, Mehta RG, Rao KVN. Retinoids and cancer in experimental animals. In: Sporn MB, Roberts AB, Goodman DS, editors. The retinoids: biology, chemistry, and medicine. New York: Raven Press; 1994. p. 573ā95.
Nowak D, Stewart D, Koeffler HP. Differentiation therapy of leukemia: 3 decades of development. Blood. 2009;113:3655ā65.
OāMalley BW, Qin J, Lanz RB. Cracking the coregulator codes. Curr Opin Cell Biol. 2008;20:310ā5.
Petrie K, Zelent A, Waxman S. Differentiation therapy of acute myeloid leukemia: past, present and future. Curr Opin Hematol. 2009;16:84ā91.
Rochette-Egly C, Germain P. Dynamic and combinatorial control of gene expression by nuclear retinoic acid receptors (RARs). Nucl Recept Signal. 2009;7, e005.
Soriano AO, Yang H, Faderl S, Estrov Z, Giles F, Ravandi F, Cortes J, Wierda WG, Ouzounian S, Quezada A, Pierce S, Estey EH, Issa JP, Kantarjian HM, Garcia-Manero G. Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome. Blood. 2007;110:2302ā8.
Spinella MJ, Kerley JS, White KA, Curtin JC. Retinoid target gene activation during induced tumor cell differentiation: human embryonal carcinoma as a model. J Nutr. 2003;133:273Sā6.
Sporn MB, Roberts AB, Goodman DS. The retinoids: biology, chemistry and medicine. 2nd ed. New York: Raven Press; 1994.
Stapnes C, Gjertsen BT, Reikvam H, Bruserud Ć. Targeted therapy in acute myeloid leukaemia: current status and future directions. Expert Opin Invest Drugs. 2009;18:433ā55.
Tanaka T, De Luca LM. Therapeutic potential of ārexinoidsā in cancer prevention and treatment. Cancer Res. 2009;69:4945ā7.
Tang X-H, Gudas LJ. Retinoids, retinoic acid receptors and cancer. Annu Rev Pathol Mech Dis. 2011;6:345ā64.
Veronesi U, Mariani L, Decensi A, Formelli F, Camerini T, Miceli R, DiMauro MG, Costa A, Marubini E, Sporn MB, DePalo G. Fifteen-year results of a randomized phase III trial of fenretinide to prevent second breast cancers. Ann Oncol. 2006;17:1065ā71.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
Ā© 2017 Springer Science+Business Media New York
About this entry
Cite this entry
Dmitrovsky, E., Spinella, M. (2017). Retinoids. In: Marshall, J. (eds) Cancer Therapeutic Targets. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0717-2_15
Download citation
DOI: https://doi.org/10.1007/978-1-4419-0717-2_15
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-0716-5
Online ISBN: 978-1-4419-0717-2
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences