DNA-PK与肿瘤放化疗敏感性的关系

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

关键词:  DNA-PK  肿瘤  放射敏感性  化学治疗  放射治疗

Key words:  DNA-PK, neoplasms, radiosensitization, chemotherapy, radiotherapy

摘要:

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。

Abstract:

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.