Exploiting the therapeutic potential of the PI3K-AKT-mTOR pathway in enriched populations of gynecologic malignancies

• Published in: Expert review of clinical pharmacology Vol. 7; no. 6; p. 847
• Main Authors: Eskander, Ramez N, Tewari, Krishnansu S
• Format: Journal Article
• Language: English
• Published: England 01-11-2014
• Subjects: Animals; Antineoplastic Agents - pharmacology; Clinical Trials, Phase II as Topic; Drug Design; Female; Genital Neoplasms, Female - drug therapy; Genital Neoplasms, Female - genetics; Genital Neoplasms, Female - pathology; Humans; Neoplasm Recurrence, Local; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; TOR Serine-Threonine Kinases - antagonists & inhibitors; PTEN; endometrial cancer; mTOR inhibitors; clear cell ovarian cancer; PI3K/AKT/mTOR pathway; cervical cancer
• ISSN: 1751-2441
• DOI: 10.1586/17512433.2014.968554

Given the prevalence of phosphatase & tensin homolog mutations in histologic specimens harvested from patients with endometrial cancer, significant interest in systemic treatment with PI3K/Akt/mTOR inhibitors has emerged. Several Phase II trials have been completed studying mTOR inhibitors in advanced/recurrent endometrial cancer. The mTOR pathway also appears to be important in some cervical cancers. Finally, because clear cell carcinoma of the ovary and renal cell carcinoma have a shared histology, the potential for activity of mTOR inhibitors in clear cell cancer of the ovary is implicit. This article reviews the results of Phase II clinical trials of PI3K/Akt/mTOR pathway inhibitors in patients with endometrial cancer, and discusses the potential therapeutic landscape of mTOR inhibition in enriched populations in gynecologic cancers.