| Literature DB >> 24310612 |
David A Nathanson1, Beatrice Gini, Jack Mottahedeh, Koppany Visnyei, Tomoyuki Koga, German Gomez, Ascia Eskin, Kiwook Hwang, Jun Wang, Kenta Masui, Andres Paucar, Huijun Yang, Minori Ohashi, Shaojun Zhu, Jill Wykosky, Rachel Reed, Stanley F Nelson, Timothy F Cloughesy, C David James, P Nagesh Rao, Harley I Kornblum, James R Heath, Webster K Cavenee, Frank B Furnari, Paul S Mischel.
Abstract
Intratumoral heterogeneity contributes to cancer drug resistance, but the underlying mechanisms are not understood. Single-cell analyses of patient-derived models and clinical samples from glioblastoma patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) demonstrate that tumor cells reversibly up-regulate or suppress mutant EGFR expression, conferring distinct cellular phenotypes to reach an optimal equilibrium for growth. Resistance to EGFR TKIs is shown to occur by elimination of mutant EGFR from extrachromosomal DNA. After drug withdrawal, reemergence of clonal EGFR mutations on extrachromosomal DNA follows. These results indicate a highly specific, dynamic, and adaptive route by which cancers can evade therapies that target oncogenes maintained on extrachromosomal DNA.Entities:
Mesh：
Substances：
Year: 2013 PMID： 24310612 PMCID： PMC4049335 DOI： 10.1126/science.1241328
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728