PI3Kα Inhibitors That Inhibit Metastasis

Oleg Schmidt-Kittler; Jiuxiang Zhu; Jian Yang; Guosheng Liu; William Hendricks; Christoph Lengauer; Sandra B. Gabelli; Kenneth W. Kinzler; Bert Vogelstein; David L. Huso; Shibin Zhou

doi:10.18632/oncotarget.166

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Research Papers:

PI3Kα Inhibitors That Inhibit Metastasis

Oleg Schmidt-Kittler, Jiuxiang Zhu, Jian Yang, Guosheng Liu, William Hendricks, Christoph Lengauer, Sandra B. Gabelli, Kenneth W. Kinzler, Bert Vogelstein, David L. Huso and Shibin Zhou _

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Oncotarget. 2010; 1:339-348. https://doi.org/10.18632/oncotarget.166

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Abstract

Received: August 18, 2010, Accepted: August 20, 2010, Published: September 11, 2010

Previous genetic analyses have suggested that mutations of the genes encoding PI3Kα facilitate invasion and metastasis but have less effect on primary tumor growth. These findings have major implications for therapeutics but have not been factored into pre-clinical drug development designs. Here we show that the inhibition of PI3Kα by newly designed small molecule inhibitors prevented metastasis formation in mice but had much less effect on the growth of subcutaneous xenografts or primary intra-abdominal tumors. These data support the idea that PI3Kα plays an important role in the metastatic process and suggest a more informed strategy for selecting drugs worthy of further development for clinical application.

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Research Papers:

PI3Kα Inhibitors That Inhibit Metastasis

Abstract