AROMATASE AND ANDROGEN INHIBITORS IN PROSTATE CANCER

前列腺癌中的芳香酶和雄激素抑制剂

• 批准号: 2087578
• 负责人: ANGELA M. BRODIE
• 金额: $ 16.55万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-09-30 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2087578
• 关键词: androgen inhibitor; androgen receptor; antineoplastics; apoptosis; aromatase; athymic mouse; biomarker; combination cancer therapy; disease /disorder model; drug design /synthesis /production; drug screening /evaluation; enzyme inhibitors; gonadotropin releasing factor; hormone related neoplasm /cancer; human tissue; laboratory rat; messenger RNA; neoplasm /cancer remission /regression; nonhuman therapy evaluation; nucleic acid probes; prostate neoplasms; steroid hormone biosynthesis; tissue /cell culture; transforming growth factors; xenotransplantation

In previous grant periods, aromatase inhibitors were developed for use in the treatment of hormone-dependent cancers. One compound, 4- hydroxyandrostenedione (4-OHA), is now being used successfully in the treatment of postmenopausal breast cancer patients. However, in preliminary studies, 4-OHA did not result in objective remission of disease in patients with metastatic prostate cancer. In an attempt to improve treatment for patients with this disease, the principal investigator has synthesized several compounds that are potent inhibitors of androgen biosynthesis (inhibiting both 17 a-hydroxylase/17,20 lyase and 5 a-reductase). They may also reduce estrogen production by limiting substrate for aromatase. The specific aims of this proposal are: 1) To synthesize and evaluate (both in vitro and in rats) steroid compounds that are more potent inhibitors of androgen biosynthesis; 2) To determine whether the most potent inhibitors cause regression of prostate cancers in the rat Dunning prostate tumor model and in athymic mice bearing PC-82 human prostate carcinoma xenografts; and 3) To determine the effects of the most potent inhibitors and newer aromatase inhibitors on androgen receptor levels and markers of programmed cell death in tumor tissue of treated mice. Effective inhibitors of androgen and estrogen biosynthesis could be of value in the treatment of prostate cancer.

在以前的拨款期间，芳香酶抑制剂被开发使用