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Retinoids and their receptors in cancer development and chemoprevention
1Department of Thoracic/Head and Neck Medical Oncology, Box 432, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ssun@notes.mdacc.tmc.edu
Abstract:
Retinoids play an important role in regulating the growth and differentiation of normal, premalignant and malignant cell types, especially epithelial cells, mainly through interaction with two types of nuclear receptors: retinoic acid receptors (RARalpha, beta and gamma) and retinoid X receptors (RXRalpha, beta and gamma). Vitamin A deficiency in experimental animals has been associated with a higher incidence of cancer and with increased susceptibility to chemical carcinogens. This is in agreement with the epidemiological studies indicating that individuals with a lower dietary vitamin A intake are at a higher risk to develop cancer. At the molecular level, aberrant expression and function of nuclear retinoid receptors have been found in various types of cancer including premalignant lesions. Thus, aberrations in retinoid signaling are early events in carcinogenesis. Retinoids at pharmacological doses exhibit a variety of effects associated with cancer prevention. They suppress transformation of cells in vitro, inhibit carcinogenesis in various organs in animal models, reduce premalignant human epithelial lesions and prevent second primary tumors following curative therapy for epithelial malignancies such as head and neck, lung, liver, and breast cancer.
Insights
Retinoids, crucial for cell growth, are vital in cancer prevention. Aberrant retinoid signaling contributes to cancer development, but pharmacological doses show promise in preventing tumors and lesions.
Area of Science:
- Oncology
- Molecular Biology
- Nutritional Science
Background:
- Retinoids regulate normal, premalignant, and malignant cell growth, particularly epithelial cells.
- Interaction with retinoic acid receptors (RARs) and retinoid X receptors (RXRs) mediates retinoid functions.
- Vitamin A deficiency and aberrant retinoid receptor expression are linked to increased cancer risk and incidence.
Purpose of the Study:
- To investigate the role of retinoids in cancer development and prevention.
- To explore the molecular mechanisms of retinoid signaling in carcinogenesis.
- To evaluate the potential of retinoids in chemoprevention and treatment of epithelial malignancies.
Main Methods:
- Analysis of retinoid signaling pathways and nuclear receptor interactions.
- Studies on vitamin A deficiency in animal models to assess cancer susceptibility.
- Epidemiological data analysis correlating dietary vitamin A intake with cancer risk.
- In vitro cell transformation assays and in vivo animal carcinogenesis models.
- Clinical studies on retinoid therapy for premalignant lesions and secondary tumor prevention.
Main Results:
- Aberrant retinoid receptor expression and function are early events in carcinogenesis.
- Vitamin A deficiency increases susceptibility to chemical carcinogens and cancer incidence.
- Retinoids at pharmacological doses suppress cell transformation and inhibit carcinogenesis in animal models.
- Retinoids reduce premalignant human epithelial lesions and prevent second primary tumors in various cancers.
Conclusions:
- Retinoid signaling plays a critical role in cancer development and prevention.
- Disruptions in retinoid signaling are implicated as early events in carcinogenesis.
- Pharmacological doses of retinoids demonstrate significant potential for cancer chemoprevention and reducing secondary tumor formation.