Targeted Therapy Resistance Mediated by Dynamic Regulation of Extrachromosomal Mutant EGFR DNA-Reference-Cited by-同舟云学术

Targeted Therapy Resistance Mediated by Dynamic Regulation of Extrachromosomal Mutant EGFR DNA

Published:2014-01-03 Issue:6166 Volume:343 Page:72-76
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Nathanson David A.¹,Gini Beatrice²,Mottahedeh Jack³,Visnyei Koppany³,Koga Tomoyuki²,Gomez German²,Eskin Ascia⁴,Hwang Kiwook⁵⁶,Wang Jun⁵⁶,Masui Kenta²,Paucar Andres¹³,Yang Huijun²,Ohashi Minori¹,Zhu Shaojun²,Wykosky Jill²,Reed Rachel²,Nelson Stanley F.⁴,Cloughesy Timothy F.⁷⁸,James C. David⁹,Rao P. Nagesh¹⁰,Kornblum Harley I.¹³⁷,Heath James R.⁵⁶,Cavenee Webster K.²¹¹,Furnari Frank B.²¹¹,Mischel Paul S.²¹¹

Affiliation:

1. Department of Molecular and Medical Pharmacology, David Geffen UCLA School of Medicine, Los Angeles, CA 90095, USA.

2. Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA, USA.

3. Neuropsychiatric Institute–Semel Institute for Neuroscience and Human Behavior and Department of Psychiatry and Biobehavioral Sciences, David Geffen UCLA School of Medicine, Los Angeles, CA 90095, USA.

4. Department of Human Genetics, David Geffen UCLA School of Medicine, Los Angeles, CA 90095, USA.

5. NanoSystems Biology Cancer Center, California Institute of Technology, Pasadena, CA, USA.

6. Division of Chemistry and Chemical Engineering, California Institute of Technology, MC 127-72, Pasadena, CA 91030, USA.

7. Henry Singleton Brain Tumor Program and Jonsson Comprehensive Cancer Center, David Geffen UCLA School of Medicine, Los Angeles, CA 90095, USA.

8. Department of Neurology, David Geffen UCLA School of Medicine, Los Angeles, CA 90095, USA.

9. University of California San Francisco, San Francisco, CA 94143, USA.

10. Department of Pathology and Laboratory Medicine, David Geffen UCLA School of Medicine, Los Angeles, CA 90095, USA.

11. UCSD School of Medicine, La Jolla, CA 92093, USA.

Abstract

Playing Hide and Seek Targeted cancer therapies have shown promising results in patients, but few of these drugs provide long-term benefits because tumor cells rapidly develop drug resistance. Nathanson et al. (p. 72 , published online 5 December) show that glioblastoma cells can become resistant to erlotinib, an epidermal growth factor receptor (EGFR)–targeted drug, by eliminating extrachromosomal copies of the mutant EGFR gene. After a period of drug withdrawal, the mutant EGFR gene reappears on extrachromosomal DNA and the tumor cells become resensitized. The discovery that cancer cells can evade drug therapy by this “hide and seek” mechanism may help to optimize the dosing schedule of erlotinib in glioblastoma patients.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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