mTOR and cancer: insights into a complex relationship.
mTOR (mammalian target of rapamycin) has come a long way since its humble beginnings as a kinase of unknown function. As part of the mTORC1 and mTORC2 complexes mTOR has key roles in several pathways that are involved in human cancer, stimulating interest in mTOR inhibitors and placing it on the radar of the pharmaceutical industry. Here, I discuss the rationale for the use of drugs that target mTOR, the unexpectedly complex mechanism of action of existing mTOR inhibitors and the potential benefits of developing drugs that function through different mechanisms. The purpose is not to cover all aspects of mTOR history and signalling, but rather to foster discussion by presenting some occasionally provocative ideas.
Sabatini
David M
DM
Whitehead Institute for Biomedical Research, MIT Department of Biology, 9 Cambridge Center, Cambridge, Massachusetts 02142-1479, USA. sabatini@wi.mit.edu
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases