The rationale for mTOR inhibition in epithelial ovarian cancer.
The AKT/mTOR signaling pathway is frequently overexpressed in human epithelial ovarian cancer and an attractive target for therapy. In vivo mouse models were confirmative for in vitro findings, where the administration of mTOR inhibitors in ovarian cancer xenografts showed antitumoral as well as antiangiogenic effects. Phase I - II trials are now ongoing with mTOR inhibitors in ovarian cancer patients, some in combination with conventional cytotoxic agents. If further development of mTOR inhibition in ovarian cancer is pursued, studying combinations of mTOR inhibitors with other new targeted therapies would be of interest. mTOR inhibitors in the adjuvant setting could have potential, since, for the moment, there is no standard maintenance therapy in ovarian cancer. A crucial challenge will be to identify strong predictive biomarkers. This review highlights the rationale for the use of mTOR inhibitors in ovarian cancer and summarizes the available preclinical findings.
Trinh
Xuan Bich
XB
St Augustinus Hospital, Translational Cancer Research Group-Antwerp, Wilrijk-Antwerp, Belgium.
van Dam
Peter A
PA
Dirix
Luc Y
LY
Vermeulen
Peter B
PB
Tjalma
Wiebren A A
WA
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects* / Q000378:metabolism; D008954:Models, Biological; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases
D000903:Antibiotics, Antineoplastic; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus