Prostate cancer is the most commonly diagnosed cancer in men. Although the cancers are initially androgen sensitive and respond to anti-hormonal therapy, over time they become refractory and grow in the absence of androgen. Such cancers, termed castrate resistant prostate cancer (CRPC), are aggressive in nature and have limited treatment options. Apart from androgens, estrogens also contribute to the initiation and progression of prostate cancer. Although estrogens are important for the normal development of the prostate gland, the estrogen receptors (ER) α and β are differentially expressed in tumors and thus offer a therapeutic target for the treatment of advanced, metastatic prostate cancer. Selective estrogen receptor modulators (SERMS) are a group of compounds that bind to ER and exert tissue specific agonist or antagonistic effects. Raloxifene, a SERM, approved for the treatment of osteoporosis in post-menopausal women, exhibits potent anti-cancer activity in in vitro and in vivo models of CRPC. However, poor bioavailability, extensive metabolism, and poor water solubility have reduced its efficacy in animal studies and clinical trials. With recent advances in nanotechnology, raloxifene has been successfully encapsulated in nanoparticles and exhibits superior pharmacokinetics than the free drug. Thus, this review has focused on the anti-cancer activity of raloxifene against CRPC, problems associated with the drug, results of clinical trials, and ways to improve raloxifene’s efficacy.
Author(s): Rhonda J. Rosengren*1, Vignesh Sundararajan2, Shuli Chen2