Editors' ChoiceCancer

Playing Hide and Seek

Science Signaling  07 Jan 2014:
Vol. 7, Issue 307, pp. ec5
DOI: 10.1126/scisignal.2005042

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. 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.

D. A. Nathanson, B. Gini, J. Mottahedeh, K. Visnyei, T. Koga, G. Gomez, A. Eskin, K. Hwang, J. Wang, K. Masui, A. Paucar, H. Yang, M. Ohashi, S. Zhu, J. Wykosky, R. Reed, S. F. Nelson, T. F. Cloughesy, C. D. James, P. N. Rao, H. I. Kornblum, J. R. Heath, W. K. Cavenee, F. B. Furnari, P. S. Mischel, Targeted therapy resistance mediated by dynamic regulation of extrachromosomal mutant EGFR DNA. Science 343, 72–76 (2014). [Abstract] [Full Text]