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Cully M, You H, Levine AJ, Mak TW.. Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer 6: 184-192

The Campbell Family Institute for Breast Cancer Research, University Health Network, University of Toronto, Toronto, Ontario M5G 2C1, Canada.
Nature reviews. Cancer (Impact Factor: 37.91). 04/2006; 6(3):184-92. DOI: 10.1038/nrc1819
Source: PubMed

ABSTRACT The tumour-suppressor phosphatase with tensin homology (PTEN) is the most important negative regulator of the cell-survival signalling pathway initiated by phosphatidylinositol 3-kinase (PI3K). Although PTEN is mutated or deleted in many tumours, deregulation of the PI3K-PTEN network also occurs through other mechanisms. Crosstalk between the PI3K pathways and other tumorigenic signalling pathways, such as those that involve Ras, p53, TOR (target of rapamycin) or DJ1, can contribute to this deregulation. How does the PI3K pathway integrate signals from numerous sources, and how can this information be used in the rational design of cancer therapies?

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    • "On the basis of this knowledge, in the last few years several potent and selective dual PIK3CA/mTOR inhibitors have been generated and carried forward into clinical trials. Unfortunately, severe rash, diarrhea and sometimes difficult to control hyperglycemia have been reported in both mice and human studies [38] [39]. Taselisib is a novel, oral, selective inhibitor of PIK3CA, which spares inhibition of PIK3-beta. "
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    • "We further observed that a high dose of TRAIL stimulates the expression of PTEN, which is required for TRAIL to induce a reduction in the levels of pMADD. Although PTEN participates in regulating apoptosis through PI3K‐Akt pathway [Cully et al., 2006], its downstream apoptotic mediators have not been fully delineated. Our present work identified MADD as a mediator of apoptotic signal emanating from PTEN. "
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