Retinoic acid belongs to a class of compounds known as retinoids, which include natural and synthetic derivatives of vitamin A. It mediates major vitamin A functions like growth and development. All-trans retinoic acid, also called ATRA or tretinoin, one form of retinoic acid, is used in treatment of acne and acute promyelocytic leukemia, a cancer of the blood and bone marrow. Retinoids can inhibit growth and induce apoptosis, a kind of cell death. They can also cause differentiation -- specialization into a particular cell type -- of breast cancer cells. These properties provide the basis for the use of retinoic acid-like compounds in breast cancer prevention studies.
Mode of Action
Retinoic acid and other retinoids diffuse freely into cells, where they bind to specific proteins called retinoic acid receptors. The retinoid-bound receptors then act in concert with other proteins to turn genes, or stretches of DNA that code for protein, on and off. More than 500 genes are regulated by retinoids, and this regulation plays an important role in growth and development, healthy immune function, normal vision and healthy skin. The retinoid-driven on-off changes in genes are also responsible for their proposed anti-cancer activity.
Sources of Retinoids
Preformed retinoids, such as retinoic acid, are found in animal sources such as fish, egg yolk, organ meats like kidney and liver, and in fortified milk. Some carotenoids -- a class of plant-derived antioxidants found in dark or yellow fruits and vegetables like carrots -- can be converted to retinoids. MayoClinic.com estimates that consumption of five servings of fruits and vegetables can provide 50 to 60 percent of the adult recommended daily allowance for vitamin A.
Use of Retinoids in Cancer
Doctors use retinoids to treat many premalignant lesions, including those in the mouth, cervix and skin. Retinoids have also been used in cancer treatment, either alone for some blood and bone marrow cancers, or combined with other agents for kidney, skin and cervical cancers. Retinoids have been used to reduce second cancer occurrence after treatment of a primary cancer in the lungs, head and neck, or liver. Despite the successful use of retinoids in prevention and treatment of specific cancers, additional studies are needed to evaluate the benefits and harms of vitamin A derivatives to cancer patients. Consult your doctor before taking any supplements.
Retinoids in Breast Cancer Prevention
The retinoid most frequently studied in cancer prevention trials, is the synthetic amide or retinoic acid called fenretinide. Clinical studies with fenretinide indicate that it may provide protection from second breast malignancies in premenopausal, but not postmenopausal, women. Other studies are evaluating the utility of fenretinide in combination with proven breast cancer prevention drugs, such as tamoxifen.
Bexarotene, a retinoid that only binds to one type of retinoic acid receptor called RXR, is being tested in a study of biomarkers -- molecules used as a disease indicator -- in women at increased risk of breast cancer.
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