mTOR and cancer: insights into a complex relationship

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Abstract
Drugs that target mTOR (mammalian target of rapamycin) have entered clinical trials for cancer treatment. However, current mTOR inhibitors have an unexpectedly complex mechanism of action. Can our emerging knowledge of this pathway be used to develop more effective mTOR-targeted therapies? 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.
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