Ciência e terapia do câncer

Targeting mTOR Complexes in Ovarian Cancer

Abstract

Seiji Mabuchi, Tomoyuki Sasano and Mahiru Kawano

The mammalian (mechanistic) target of rapamycin (mTOR) is a serine/threonine kinase that plays a key role in cell growth and proliferation and is regarded as an attractive therapeutic target for cancer therapy. Preclinical investigations have suggested that mTOR complex 1 (mTORC1) and mTORC2 are frequently activated in epithelial ovarian cancer, especially in clear cell carcinoma of the ovary. In mouse models of ovarian cancer, mTORC1 inhibitors have demonstrated promising antitumor activity against ovarian cancer both in the setting of monotherapy and when used in combination with cytotoxic agents. Based on these promising preclinical findings, mTORC1 inhibitors are currently being evaluated in phase I/II trials involving ovarian cancer patients. In an effort to overcome resistance to mTORC1 inhibitors, novel mTOR kinase inhibitors (TORKinib) that inhibit both mTORC1 and mTORC2 have recently been developed. In this report, we review the scientific rationale and evidence for the potential clinical benefits provided by mTOR inhibitors in patients with epithelial ovarian cancer.