Development of a Novel Tissue Specific Aromatase Activity Regulation Therapeutic Method

摘要

Estrogen is essential for normal growth and development of the female reproductive system and breast. Lifetime exposure to estrogen may affect a woman's risk for breast cancer. Approximately 70% of breast cancers are estrogen receptor (ER) positive and adjuvant antiestrogen therapy is considered as a primary therapy for those cancer patients. In the past 2 decades, selective estrogen receptor modulators (SERMs), especially tamoxifen, have been clinically used. Although tamoxifen is a powerful blocking drug for estrogen receptor in breast cancer tissue, it is also known as a weak estrogen signal stimulator in other organs such as liver, bone and uterine. As such it is now believed that tamoxifen can slightly increase the risk of uterine cancer. While tamoxifen has been clinically used as the first line therapeutic drug, many researchers, including our research group, were developing drugs that would inhibit the production of estrogen. Estrogen is produced by the ovaries and other tissues of the body using an enzyme called aromatase. Once women have reached menopause, the ovaries no longer produce estrogen. Therefore, particularly in postmenopausal women with breast cancer, estrogen production in the breast tissue can regulate the cancer growth. Currently, the third generation of aromatase inhibitors (AIs), such as exemestane (Aromasin(trademark)), anastrazole (Arimidex(trademark)) and letrozole (Femera(trademark)), are approved by US. Food and Drug Administration and clinically used for those estrogen sensitive breast cancer patients with postmenopausal women.