MYCing and YAPing the escape of tumor cell growth arrest after chronic PI3K/mTOR inhibition

The phosphatidylinositol-3-kinase (PI3K)/Akt and mammalian target of rapamycin (mTOR) signaling cascades represent two critical and highly interconnected pathways regulating cellular proliferation, metabolism, differentiation and survival—particularly in response to cytotoxic stress (1). As a single pathway exploited by multiple neoplasms, mutations of PI3K/mTOR’s components represent attractive pharmacological targets, leading to the development of a wide array of targeted therapies (2).