Double PIK3CA mutations in cis increase oncogenicity and sensitivity to PI3Kα inhibitors
نویسندگان
چکیده
منابع مشابه
PIK3CA/PTEN mutations and Akt activation as markers of sensitivity to allosteric mTOR inhibitors.
PURPOSE We sought to determine whether phosphoinositide 3-kinase (PI3K) pathway mutation or activation state and rapamycin-induced feedback loop activation of Akt is associated with rapamycin sensitivity or resistance. EXPERIMENTAL DESIGN Cancer cell lines were tested for rapamycin sensitivity, Akt phosphorylation, and mTOR target inhibition. Mice injected with breast or neuroendocrine cancer...
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Purpose: We describe herein a novel P447_L455 deletion in the C2 domain of PIK3CA in a patient with an ER+ breast cancer with an excellent response to the PI3Kα inhibitor alpelisib. Although PIK3CA deletions are relatively rare, a significant portion of deletions cluster within amino acids 446-460 of the C2 domain, suggesting these residues are critical for p110α function.Experimental Design: A...
متن کاملPredictive Biomarkers and Personalized Medicine PIK3CA/PTEN Mutations and Akt Activation As Markers of Sensitivity to Allosteric mTOR Inhibitors
Purpose: We sought to determine whether phosphoinositide 3-kinase (PI3K) pathway mutation or activation state and rapamycin-induced feedback loop activation of Akt is associated with rapamycin sensitivity or resistance. Experimental Design: Cancer cell lines were tested for rapamycin sensitivity, Akt phosphorylation, and mTOR target inhibition. Mice injected with breast or neuroendocrine cancer...
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PI3Kα-selective inhibitor BYL719 is currently in phase II/III clinical trial for the treatment of breast cancer, but highly variable response has been observed among patients. We sought to discover predictive biomarker for the efficacy of BYL719 by dissecting the proliferative signaling pathway mediated by PI3K in breast cancer. BYL719 concurrently inhibited the phosphorylation of AKT and ERK i...
متن کاملPI3Kα Inhibitors That Inhibit Metastasis
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 metastasi...
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ژورنال
عنوان ژورنال: Science
سال: 2019
ISSN: 0036-8075,1095-9203
DOI: 10.1126/science.aaw9032