PARP抑制剂在恶性肿瘤中的应用及耐药研究进展

Research progress of PARP inhibitors in cancers and their drug resistance

聚腺苷二磷酸核糖聚合酶-1(PARP-1)在生物体中发挥着强大的生理功能,包括DNA损伤修复,维持基因组稳定性,调节细胞增殖、分化、死亡,等。目前PARP抑制剂在乳腺癌易感基因BRCA1/2突变的肿瘤如乳腺癌、卵巢癌、前列腺癌和胰腺癌中得到了广泛应用。但对于其他恶性肿瘤以及对PARP抑制剂产生耐药的人群,PARP抑制剂有一定的局限性。本文通过分析总结PARP抑制剂在肺癌、肝细胞癌、胶质母细胞瘤、白血病及宫颈癌中的临床前及临床研究进展,同时针对PARP抑制剂耐药情况,总结其与其他抗肿瘤药物如DNA损伤修复抑制剂、免疫检查点抑制剂、抗血管生成药物以及其他化疗药物联用解决耐药的策略,为未来PARP抑制剂的临床应用提供参考依据。

Poly ADP-ribose polymerase-1(PARP-1)plays a vital role in organisms,including regulating repair of DNA,maintaining genome stability,regulating cell proliferation,differentiation,and death.At present,PARP inhibitors have been made some breakthrough in the treatment of breast cancer,ovarian cancer,prostate cancer and pancreatic cancer.However,PARP inhibitors have certain limitations in other malignant tumors and patients who are resistant to PARP-1 inhibitors.This article summarizes the research on PARP inhibitors in lung cancer,hepatocellular carcinoma,glioblastoma,leukemia and cervical cancer,and introduces the strategies of combining other anti-tumor drugs such as DNA repair inhibitors,immune checkpoint inhibitors,anti-angiogenic drugs and other chemotherapeutic drugs to solve their drug resistance,which provides some reference for the wide clinical application of PARP inhibitors in the future.