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PI3K pathway alterations in cancer: variations on a theme

Abstract

The high frequency of phosphoinositide 3-kinase (PI3K) pathway alterations in cancer has led to a surge in the development of PI3K inhibitors. Many of these targeted therapies are currently in clinical trials and show great promise for the treatment of PI3K-addicted tumors. These recent developments call for a re-evaluation of the oncogenic mechanisms behind PI3K pathway alterations. This pathway is unique in that every major node is frequently mutated or amplified in a wide variety of solid tumors. Receptor tyrosine kinases upstream of PI3K, the p110α catalytic subunit of PI3K, the downstream kinase, AKT, and the negative regulator, PTEN, are all frequently altered in cancer. In this review, we will examine the oncogenic properties of these genetic alterations to understand whether they are redundant or distinct and propose treatment strategies tailored for these genetic lesions.

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Acknowledgements

We thank K Courtney, M Saelzler and C Benes for insightful discussions and critical reading of the paper. This research was supported by funding to LCC from the National Institutes of Health and to TLY from a Dana-Farber/Harvard Cancer Center SPORE (1P50CA127003-01).

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Correspondence to L C Cantley.

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Yuan, T., Cantley, L. PI3K pathway alterations in cancer: variations on a theme. Oncogene 27, 5497–5510 (2008). https://doi.org/10.1038/onc.2008.245

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