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The PI3K-AKT-mTOR pathway is the subject of intense clinical investigation, particularly in ER-positive breast cancer. Mutations along this pathway are thought to contribute to the development of endocrine resistance. In the last few years, novel strategies to overcome resistance have resulted in positive clinical trials partnering endocrine therapy with targeted agents such as the mTOR inhibitor everolimus and the PI3K inhibitor alpelisib. These drugs are now FDA approved, and numerous clinical trials are ongoing to evaluate other agents that might affect this pathway.
The mTOR kinase is distal to PI3K-ADT signaling and actually comprises two distinct complexes: mammalian target of rapamycin complex 1 and 2 (mTORC1, mTORC2). The currently a…