PARP抑制剂在乳腺癌中的临床应用

Clinical application of PARP inhibitors in breast cancer

多腺苷二磷酸核糖聚合酶(PARP)抑制剂通过抑制DNA损伤修复,导致同源重组修复缺陷(HRD)的肿瘤合成致死。目前已有两种PARP抑制剂奥拉帕利和他拉唑帕利获批用于乳腺癌易感基因(BRCA)突变、人类表皮生长因子受体2(HER2)阴性晚期乳腺癌的挽救治疗和早期乳腺癌的辅助治疗。PAPR抑制剂单药表现出良好的抗肿瘤活性和可控的安全性。PAPR抑制剂联合化疗、放疗、抗血管治疗及免疫治疗等多项临床研究正在开展,PARP抑制剂的适应证也由BRCA突变延伸至HRD,从卵巢癌和乳腺癌扩展到其他实体瘤,将来有希望能惠及更多的肿瘤患者。

Poly adenosine diphosphate ribose polymerase(PARP)inhibitors lead to synthetic lethality in homologous recombination repair-deficient(HRD)tumors by inhibiting DNA damage repair.Two PARP inhibitors,olaparib and talazoparib,have been approved for the salvage treatment of breast cancer susceptibility gene(BRCA)mutation,human epidermal growth factor receptor 2(HER2)negative advanced breast cancer,and adjuvant treatment of early breast cancer.PAPR inhibitor single agent shows good antitumor activity and controllable safety.A number of clinical studies on PAPR inhibitors combined with chemotherapy,radiotherapy,antiangiogenic therapy and immunotherapy are being carried out.The indications of PARP inhibitors also extend from BRCA mutation to HRD,from ovarian cancer and breast cancer to other solid tumors,promising to benefit more patients in the future.