DNA-PK与肿瘤放化疗敏感性的关系

辐射或药物损伤可致肿瘤细胞DNA双链断裂,而DNA依赖性蛋白激酶(DNA-depended protein kinase,DNA-PK)是DNA损伤修复的关键酶,决定着受损肿瘤细胞的转归.因此,DNA-PK与肿瘤放化疗敏感性的关系成为研究热点.近年来,关于DNA-PK的结构与功能、在肿瘤细胞株中的活性、在肿瘤组织中的表达的研究日益深入,以DNA-PK为靶点的DNA修复抑制剂作为肿瘤放化疗增敏药已陆续研发并进入临床前试验.该综述简要回顾DNA-PK的生物学作用及其研究进展.

Correlations between DNA-PK and radio/chemo-sensitization of tumor

DNA double-strand breaks(DSBs) are the major lethal lesions in tumor cells induced by ionizing radiation and chemotherapy.DNA-depended protein kinase(DNA-PK) was considered a critical enzyme in the repair of the DSBs,determining the survival of lethal tumor cells.Activity of DNA-PK,whether in human tumor cell lines or in primary tumor biopsies from patients,was shown to be important for tumor response to radiation,so correlations between DNA-PK protein expression and treatment outcome become a hot spot for research.Today,with its specific structure and function,DNA-PK proves a viable target for radio-sensitization and chemo-sensitization.DNA-PK inhibitors,a kind of novel radiation-sensitizing drugs,were developed and came to pre-clinical trial.This is a review about DNA-PK and its application in radio/chemo-sensitization of tumor.