Targeting mTOR Signaling Pathway in Ovarian Cancer

S.      Mabuchi; T.      Hisamatsu; T.      Kimura

Abstract

The mammalian target of rapamycin (mTOR) is frequently activated in epithelial ovarian cancer, and is regarded as an attractive therapeutic target for therapy. Preclinical investigations using rapamycin and its analogs have demonstrated significant growthinhibitory effects on the growth of ovarian cancer both in the setting of monotherapy and in combination with cytotoxic agents. Based on promising preclinical data, mTOR inhibitors are currently being evaluated in several phase I/II trials in patients with ovarian cancer. In an effort to overcome resistance to rapamycin and its analogs, the novel ATP-competitive mTOR inhibitors have recently been developed. In this report, we review the scientific rationale and evidence for the potential clinical benefits provided by mTOR inhibitor therapy for patients with epithelial ovarian cancer.

Keywords: mTOR, mTORC1, mTORC2, AKT, ovarian cancer, rapamycin, rapalogs, everolimus, temsirolimus, ATP-competitive mTOR inhibitors