Abstract
HER2 amplification and PIK3CA mutation were validated as biomarkers for sensitivity to the single-agent phosphoinositide 3-kinase (PI3K) inhibitor, GDC-0941, in breast cancer models. A novel expression profile was developed to identify other breast cancers sensitive to PI3K inhibitors. These expression studies highlighted feedback networks connecting TORC1, PI3K, and mitogen-activated protein kinase (MAPK) pathways, and underscored the potential for combination therapies.
Copyright 2010 AACR.
MeSH terms
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Animals
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Biomarkers, Tumor / antagonists & inhibitors
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism
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Disease Models, Animal
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Female
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Gene Expression Profiling
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Humans
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Indazoles / pharmacology*
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Mice
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Mitogen-Activated Protein Kinases / metabolism
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Mutation
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Phosphatidylinositol 3-Kinase / genetics
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Phosphatidylinositol 3-Kinase / metabolism
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Phosphoinositide-3 Kinase Inhibitors*
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Receptor, ErbB-2 / metabolism
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Sulfonamides / pharmacology*
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Transcription Factors / metabolism
Substances
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2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine
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Biomarkers, Tumor
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CRTC1 protein, human
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Indazoles
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Phosphoinositide-3 Kinase Inhibitors
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Sulfonamides
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Transcription Factors
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Phosphatidylinositol 3-Kinase
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ERBB2 protein, human
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Receptor, ErbB-2
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Mitogen-Activated Protein Kinases