Mammalian target of rapamycin (mTOR) is the hub of the phosphoinositide
3-kinase (PI3K)/Akt/mTOR pathway, which is one of the most commonly mutated
pathways in cancer. mTOR is considered a member of the PI3K-kinase-related kinase
(PIKK) superfamily since its C-terminus shares strong homology to the catalytic
domain of PI3K. Currently it is known that mTOR functions as two complexes, mTOR
complex 1 (mTORC1) and mTORC2. Clinically used rapamycin and rapalogs are
allosteric inhibitors of mTORC1 and effective as anticancer agents in various
preclinical models. In clinical trials, rapalogs have demonstrated efficacy against certain
types of cancer. Recently, a new generation of mTOR inhibitors, which compete with
ATP in the catalytic site of mTOR and inhibit both mTORC1 and mTORC2 with a high
degree of selectivity, have been developed. Besides, some natural products, such as
epigallocatechin gallate (EGCG), caffeine, curcumin, resveratrol and cryptotanshinone,
have been found to inhibit mTOR as well. Here, we review the current findings
regarding mTOR signaling pathway and discuss the advances in mTOR inhibitors as
anticancer agents.
Keywords: mTOR, mTORC1, mTORC2, inhibitor, rapamycin, rapalogs.