Molecular pathways: current role and future directions of the retinoic acid pathway in cancer prevention and treatment.

Abstract

Retinoids and their naturally metabolized and synthetic products (e.g., all-trans retinoic acid, 13-cis retinoic acid, bexarotene) induce differentiation in various cell types. Retinoids exert their actions mainly through binding to the nuclear retinoic acid receptors (α, β, γ), which are transcriptional and homeostatic regulators with functions that are often compromised early in neoplastic transformation. The retinoids have been investigated extensively for their use in cancer prevention and treatment. Success has been achieved with their use in the treatment of subtypes of leukemia harboring chromosomal translocations. Promising results have been observed in the breast cancer prevention setting, where fenretinide prevention trials have provided a strong rationale for further investigation in young women at high risk for breast cancer. Ongoing phase III randomized trials investigating retinoids in combination with chemotherapy in non-small cell lung cancer aim to definitively characterize the role of retinoids in this tumor type. The limited treatment success observed to date in the prevention and treatment of solid tumors may relate to the frequent epigenetic silencing of RARβ. Robust evaluation of RARβ and downstream genes may permit optimized use of retinoids in the solid tumor arena.

• Authors: Roisin M Connolly, Nguyen K Nguyen, Saraswati Sukumar
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 19 Issue 7 Pg. 1651-9 (Apr 01 2013) ISSN: 1557-3265 [Electronic] United States
• PMID: 23322901 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Review)
• Copyright: ©2013 AACR.

Chemical References

• Antineoplastic Agents
• Receptors, Retinoic Acid
• Retinoids
• Tretinoin

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Drug Resistance, Neoplasm (genetics)
• Humans
• Neoplasms (drug therapy, metabolism, prevention & control)
• Receptors, Retinoic Acid (genetics, metabolism)
• Retinoids (pharmacology, therapeutic use)
• Signal Transduction (drug effects)
• Translational Research, Biomedical
• Tretinoin (metabolism)