title: Exploiting the therapeutic potential of the PI3K-AKT-mTOR pathway in enriched populations of gynecologic malignancies.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of California Irvine Medical Center, Building 56 Room 260, 101 The City Drive South, Orange CA 92868 USA.
authors.forename: Ramez N
authors.initials: RN
authors.lastname: Eskander
authors.forename: Krishnansu S
authors.initials: KS
authors.lastname: Tewari
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017322:Clinical Trials, Phase II as Topic; D015195:Drug Design; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D009364:Neoplasm Recurrence, Local; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: PI3K/AKT/mTOR pathway; PTEN; cervical cancer; clear cell ovarian cancer; endometrial cancer; mTOR inhibitors