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Sci Rep. 2015 Jun 11;5:11305. doi: 10.1038/srep11305.

The EGFR mutation status affects the relative biological effectiveness of carbon-ion beams in non-small cell lung carcinoma cells.

Author information

1
1] Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan [2] Department of Radiology, Chulalongkorn University, Pathumwan, Bangkok, Thailand.
2
1] Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan [2] Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
3
Advanced Scientific Research Leaders Development Unit, Gunma University, Maebashi, Gunma, Japan.
4
Department of Oncologic Sciences, Mitchell Cancer Institute, Alabama, USA.
5
Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
6
Tottori University Hospital Cancer Center, Yonago, Tottori, Japan.
7
Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
8
Gunma University Heavy Ion Medical Center, Maebashi, Gunma, Japan.

Abstract

Carbon-ion radiotherapy (CIRT) holds promise to treat inoperable locally-advanced non-small cell lung carcinoma (NSCLC), a disease poorly controlled by standard chemoradiotherapy using X-rays. Since CIRT is an extremely limited medical resource, selection of NSCLC patients likely to benefit from it is important; however, biological predictors of response to CIRT are ill-defined. The present study investigated the association between the mutational status of EGFR and KRAS, driver genes frequently mutated in NSCLC, and the relative biological effectiveness (RBE) of carbon-ion beams over X-rays. The assessment of 15 NSCLC lines of different EGFR/KRAS mutational status and that of isogenic NSCLC lines expressing wild-type or mutant EGFR revealed that EGFR-mutant NSCLC cells, but not KRAS-mutant cells, show low RBE. This was attributable to (i) the high X-ray sensitivity of EGFR-mutant cells, since EGFR mutation is associated with a defect in non-homologous end joining, a major pathway for DNA double-strand break (DSB) repair, and (ii) the strong cell-killing effect of carbon-ion beams due to poor repair of carbon-ion beam-induced DSBs regardless of EGFR mutation status. These data highlight the potential of EGFR mutation status as a predictor of response to CIRT, i.e., CIRT may show a high therapeutic index in EGFR mutation-negative NSCLC.

PMID:
26065573
PMCID:
PMC4463964
DOI:
10.1038/srep11305
[Indexed for MEDLINE]
Free PMC Article

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