PD-1/PD-L1抑制剂与PARP抑制剂联用:三阴乳腺癌治疗新视角

Combining PD-1/PD-L1 inhibitor and PARP inhibitor:a new perspective on the treatment of triple negative breast cancer

三阴乳腺癌相对于其他类型乳腺癌,由于本身高度侵袭性和缺乏有效治疗靶点,因此其生存预后较差。免疫检测点(PD-1/PD-L1和CTL-4)抑制剂在治疗各种转移性肿瘤取得突破性成功。PARP抑制剂可促进肿瘤细胞DNA损伤,不仅通过一系列分子机制促进免疫启动,还可导致程序性死亡配体1 (PD-L1)表达的适应性上调。故两者联用可以提高肿瘤疗效。本文综述了它们在三阴乳腺癌联用的研究进展,并且提出相关的进一步发展的思路,希望寻找两者联用的最佳治疗模式。

Patients with TNBC typically have a relatively poorer outcome compared with those withother breast cancer subtypes owing to an inherently aggressive clinical behaviour and a lack of recognized molecular targets for therapy. Immune checkpoint (PD-1/PD-L1 and CTL-4)inhibitors have emerged as a breakthrough therapy in the treatment in various metastatic cancers. PARP inhibitors drive increased DNA damage of tumor cells, which not only promotes immune priming through a range ofmolecular mechanisms, but also leads to adaptive upregula-tion of programmed death ligand 1 (PD-L1) expression. Therefore, PD-1/PD-L1 inhibitors combined with Parp inhibitors can improve the efficacy of tumor treatment. We reviewed the research progress of their combined use in triple-negative breast cancer, and put forward relevant ideas for further development, hoping to find the best treatment mode of the combined use of the two.