[Strategy of drug development for hormone-dependent tumor].
It is established that estrogen and androgen facilitate the proliferation of breast and prostate cancers. Hormonal therapy for these tumors using agents which inhibit hormone synthesis (inhibitors of aromatase and lyase) or bind hormone receptor have been used. However, some patients become resistant gradually during the hormonal therapy. Furthermore, QOL of patients was impaired by the side effects associated with the therapy, such as decreases in bone density, libido, and potency. The osteoporosis is a potential concern with the prolonged use of antiestrogen. The beneficial effect of estrogen receptor antagonist, tamoxifen on breast cancer has been established, but this agent may increase the proliferation of endometrium, which may increase the incidence of uterine cancer. Tamoxifen is a partial agonist, leading to the increase in transcriptional activity. Recently, ICI-164.384 is reported to be a pure antagonist and effective in tamoxifen-refractory tumor. Hopefully, pure antiandrogen will be available in the near future. There are reports suggesting that several specific and tissue-specific factors are involved in transcriptional activity of sex steroid hormone receptors. It is likely that these factors are novel targets for drugs which have a high potency and organ-or tissue-selective antagonist of sex steroid hormone for the treatment of hormone-dependent cancers.
Kudoh
M
M
Endocrinology & Metabolic Disease Research Laboratory, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd. Tsukuba, Japan.
D000726:Androgen Antagonists / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy; D004958:Estradiol / Q000031:analogs & derivatives / Q000627:therapeutic use; D004965:Estrogen Antagonists / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D053284:Polyunsaturated Alkamides; D011471:Prostatic Neoplasms / Q000188:drug therapy; D013629:Tamoxifen / Q000627:therapeutic use
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D053284:Polyunsaturated Alkamides; D013629:Tamoxifen; D004958:Estradiol; C051781:ICI 164384