Current development of mTOR inhibitors as anticancer agents.
Mammalian target of rapamycin (mTOR) is a kinase that functions as a master switch between catabolic and anabolic metabolism and as such is a target for the design of anticancer agents. The most established mTOR inhibitors--rapamycin and its derivatives--showed long-lasting objective tumour responses in clinical trials, with CCI-779 being a first-in-class mTOR inhibitor that improved the survival of patients with advanced renal cell carcinoma. This heralded the beginning of extensive clinical programmes to further evaluate mTOR inhibitors in several tumour types. Here we review the clinical development of this drug class and look at future prospects for incorporating these agents into multitarget or multimodality strategies against cancer.
Faivre
Sandrine
S
Service Inter Hospitalier de Cancrologie, Beaujon University Hospital, 100 Boulevard du General Leclerc, 92118 Clichy Cedex, France.
Kroemer
Guido
G
Raymond
Eric
E
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018797:Cell Cycle Proteins; D019008:Drug Resistance, Neoplasm; D044127:Epigenesis, Genetic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D051059:PTEN Phosphohydrolase / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011494:Protein Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C087000:EIF4EBP1 protein, human; C546842:MTOR protein, human