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Role of retinoid receptors in the prevention and treatment of breast cancer.
Yang LM, Tin-U C, Wu K, Brown P
Department of Medicine, The University of Texas Health Science Center at San
Antonio, 78284, USA.
Retinoids are vitamin A-related compounds that have been found to prevent
cancer in animals and humans. In this review, we discuss the role of
retinoids and their receptors in the treatment and prevention of breast
cancer. The retinoid receptors are expressed in normal and malignant breast
cells, and are critical for normal development. In breast cells, when bound
by retinoid hormones, these proteins regulate proliferation, apoptosis, and
differentiation.
The mechanism by which retinoids inhibit breast cell growth
has not been completely elucidated, however, retinoids have been shown to
affect multiple signal transduction pathways, including IGF-, TGFbeta-, and
AP-1-dependent pathways. Retinoids have also been shown to suppress the
growth and prevent the development of breast cancer in animals. These agents
suppress tumorigenesis in carcinogen-treated rats and in transgenic mice, and
inhibit the growth of transplanted breast tumors.
These promising preclinical
results have provided the rationale to test retinoids in clinical trials for
the treatment and prevention of breast cancer. Several retinoids, including
all trans retinoic acid and 9-cis retinoic acid, have been shown to have
modest activity in the treatment of breast cancer, and these agents are now
in clinical trials in combination with cytotoxic agents and anti-estrogens.
Another retinoid, 4-HPR, is currently being tested in a human cancer
prevention trial. Preliminary results suggest that 4-HPR may suppress breast
cancer development in premenopausal women.
Future clinical trials will focus
on testing new synthetic retinoids that have reduced toxicity and enhanced
therapeutic and preventive efficacy.
J Mammary Gland Biol Neoplasia 1999 Oct;4(4):377-88
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