Discovery of Drug-Resistant and Drug-Sensitizing Mutations in the Oncogenic PI3K Isoform p110α

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Discovery of drug-resistant and drug-sensitizing mutations in the oncogenic PI3K isoform p110 alpha.

p110 alpha (PIK3CA) is the most frequently mutated kinase in human cancer, and numerous drugs targeting this kinase are currently in preclinical development or early-stage clinical trials. Clinical resistance to protein kinase inhibitors frequently results from point mutations that block drug binding; similar mutations in p110 alpha are likely, but currently none have been reported. Using a S. ...

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Oncogenic Mutations of p110α Isoform of PI 3-Kinase Upregulate Its Protein Kinase Activity

In addition to lipid kinase activity, the class-I PI 3-kinases also function as protein kinases targeting regulatory autophosphorylation sites and exogenous substrates. The latter include a recently identified regulatory phosphorylation of the GM-CSF/IL-3 βc receptor contributing to survival of acute myeloid leukaemia cells. Previous studies suggested differences in the protein kinase activity ...

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ژورنال

عنوان ژورنال: Cancer Cell

سال: 2008

ISSN: 1535-6108

DOI: 10.1016/j.ccr.2008.06.014