Future directions in the treatment of hormone-sensitive advanced breast cancer: the RAD001 (Everolimus)-letrozole clinical program.

摘要: Therapeutics that interfere with estrogen receptor function (antiestrogens, eg, tamoxifen; aromatase inhibitors, letrozole) have contributed to a dramatic reduction in breast cancer mortality; however, not all estrogen-receptor-positive cancers respond. The mammalian target-of-rapamycin (mTOR) is emerging as an important target molecule the treatment of cancer. Furthermore, activation growth-factor signaling pathways involve mTOR may contribute both failure endocrine therapy well development resistance. RAD001 (everolimus) potent, orally bioavailable inhibitor pathway. Preclinical data show effectively inhibits proliferation and growth number cell lines vitro range tumor types experimental animal models Moreover, exhibits antiangiogenic activity, which also its anticancer activity. letrozole potent for acts inhibit aromatization androgens, thereby reducing plasma levels. Combining rational approach advanced cancer, offering potential inhibition growth/proliferation angiogenesis while at same time potentially preventing data, derived from aromatase-expressing, models, suggest synergistic interaction between results more profound effects on induction death. Importantly, early clinical no pharmacokinetic or increase toxicity combined treatment, compared alone, there evidence antitumor Enrollment into phase II studies presently underway.