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F1000Prime Rep. 2015 Feb 3;7:13. doi: 10.12703/P7-13. eCollection 2015.

The phosphoinositide 3-kinase pathway and therapy resistance in cancer.

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Department of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School 330 Brookline Avenue, EC/CLS 633A, Boston, MA 02215 USA.


The phosphoinositide 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling network is a master regulator of processes that contribute to tumorigenesis and tumor maintenance. The PI3K pathway also plays a critical role in driving resistance to diverse anti-cancer therapies. This review article focuses on mechanisms by which the PI3K pathway contributes to therapy resistance in cancer, and highlights potential combination therapy strategies to circumvent resistance driven by PI3K signaling. In addition, resistance mechanisms that limit the clinical efficacy of small molecule inhibitors of the PI3K pathway are discussed.

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