Enhancing Hormonal Therapy for Breast Cancer by Combination with a Well- Known Approved Pharmaceutical with Little Toxicity

摘要

The beneficial effects of hormonal therapy with antiestrogens or aromatase inhibitors for estrogen receptor (ER) positive metastatic breast cancer are limited by the phenomenon of hormonal resistance. We have found that valproic acid (VPA), a pharmaceutical long used as an anti-convulsant and recently found to have anti-tumor action possibly because it is a histone deacetylase inhibitor, enhances the action of antiestrogens and aromatase inhibitors on breast cancer cells. Our specific hypothesis is that VPA, will enhance the effectiveness and duration of hormonal therapy of human breast cancer xenografts growing in mice and with few side effects. Thus VPA would be an immediate candidate as an agent to enhance the effectiveness of hormonal therapy in humans. In the first few months of this award we have begun to investigate the ability of VPA to enhance the actions of tamoxifen or letrozole on human breast cancer xenografts growing on nude mice. We have also begun planning a human clinical trial of the ability of VPA to enhance tamoxifen action during a two week treatment after biopsy and prior to surgery.