mTOR and Various Cancers

The evolutionarily conserved kinase, mTOR, is distributed in two protein complexes, mTORC1 and mTORC2, which play a critical role in regulating cell growth, proliferation, migration and survival. Numerous upstream genetic alterations converge on mTOR, leading to its hyperactivation in a broad spectrum of human cancers. However, the clinical evaluation of the mTORC1 inhibitor, rapamycin, in treating cancers has yielded disappointing results, which is due in part to rapidly developed resistance to the drug. To improve on rapamycin therapies, understanding how resistance occurs, identifying new therapeutic targets for future drug development, and revealing new biomarkers to improve on current assays used to monitor disease progression, are all needed. In order to accomplish these tasks, Dr. Yu team has taken a global phospho-proteomic approach towards defining the signaling landscape downstream of both mTORC1 and mTORC2. Together, the scientists of Dr. Yu team have been working on identification of new mechanisms for rapamycin resistance that provides opportunities for improving therapy, identification of possible tumor suppressors, and contribution to the entire research community with many new mTOR targets that will seed the discovery of new mechanisms that contribute to mTOR-mediated tumorigenesis, and thus new therapeutic strategies.