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Drug discovery approaches targeting the PI3K/Akt pathway in cancer

Oncogene volume 27, pages 5511–5526 (2008)Cite this article

Abstract

The abnormal activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway has been validated by epidemiological and experimental studies as an essential step toward the initiation and maintenance of human tumors. Notable in this regard are the prevalent somatic genetic alterations leading to the inactivation of the tumor suppressor gene PTEN and gain-of-function mutations targeting PIK3CA—the gene encoding the catalytic phosphosinositide-3 kinase subunit p110α. A number of the intracellular components of this pathway have been targeted as anticancer drug discovery activities leading to the current panoply of clinical trials of inhibitors of PI3K, Akt and HSP90 in man. This review summarizes current preclinical knowledge of modulators of the PI3K/Akt pathway in which drug discovery and development activities have been advanced focusing on both the relevant clinical stage inhibitors and other disclosed tool compounds targeting PI3K, PDK1, Akt and HSP90.

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  1. Oncology Drug Discovery, Novartis Institutes for Biomedical Research, Basel, Switzerland

    C Garcia-Echeverria

  2. Novartis Institutes for Biomedical Research, Cambridge, MA, USA

    W R Sellers

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  1. C Garcia-Echeverria
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  2. W R Sellers
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Correspondence to C Garcia-Echeverria.

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Garcia-Echeverria, C., Sellers, W. Drug discovery approaches targeting the PI3K/Akt pathway in cancer. Oncogene 27, 5511–5526 (2008). https://doi.org/10.1038/onc.2008.246

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