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PI3Kα Inhibitors That Inhibit Metastasis

2010; Impact Journals LLC; Volume: 1; Issue: 5 Linguagem: Inglês

10.18632/oncotarget.166

1949-2553

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

Advanced Breast Cancer Therapies

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.