Src Mutation Induces Acquired Lapatinib Resistance in ERBB2-Amplified Human Gastroesophageal Adenocarcinoma Models

• Published in: PloS one Vol. 9; no. 10; p. e109440
• Main Authors: Hong, Yong Sang, Kim, Jihun, Pectasides, Eirini, Fox, Cameron, Hong, Seung-Woo, Ma, Qiuping, Wong, Gabrielle S., Peng, Shouyong, Stachler, Matthew D., Thorner, Aaron R., Van Hummelen, Paul, Bass, Adam J.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.10.2014; Public Library of Science (PLoS)
• Subjects: 1-Phosphatidylinositol 3-kinase; Adenocarcinoma; Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Amplification; Antineoplastic Agents - pharmacology; Benzodioxoles - pharmacology; Biology and Life Sciences; Breast cancer; Cancer therapies; Cell culture; Cell cycle; Cell Line, Tumor; Chemotherapy; Clinical medicine; DNA Mutational Analysis; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm - genetics; Ectopic expression; Epidermal growth factor; ErbB-2 protein; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - genetics; Esophagus; Gene Amplification; Gene Expression; Gene Silencing; Genes, src; Genomes; Humans; Inhibition; Inhibitor drugs; Kinases; Medicine; Medicine and Health Sciences; Metastases; Metastasis; Mutation; Oncology; Pharmacology; Phosphorylation; Protein kinase; Protein Kinase Inhibitors - pharmacology; Quinazolines - pharmacology; Receptor, ErbB-2 - genetics; RNA Interference; Src protein; Stomach Neoplasms - drug therapy; Stomach Neoplasms - genetics; Targeted cancer therapy; Therapy; Tumors; United States > US; Massachusetts

ERBB2-directed therapy is now a routine component of therapy for ERBB2-amplified metastatic gastroesophageal adenocarcinomas. However, there is little knowledge of the mechanisms by which these tumors develop acquired resistance to ERBB2 inhibition. To investigate this question we sought to characte...