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

摘要: 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 benefit from it important; however, biological predictors response are ill-defined. The present study investigated the association between mutational status EGFR and KRAS, driver genes frequently mutated in NSCLC, relative effectiveness (RBE) carbon-ion beams over assessment 15 lines different EGFR/KRAS that isogenic expressing wild-type or mutant revealed EGFR-mutant cells, but not KRAS-mutant show low RBE. This was attributable (i) high X-ray sensitivity since mutation associated with defect non-homologous end joining, major pathway for DNA double-strand break (DSB) repair, (ii) strong cell-killing effect due poor repair beam-induced DSBs regardless status. These data highlight potential as predictor CIRT, i.e., may therapeutic index mutation-negative NSCLC.