【摘要】 复制应激(replication stress, RS)是指由于各种因素导致DNA复制叉的推进受阻、停滞或崩溃,这会激活细胞复制应激反应来应对复制应激,但是如果复制应激超过细胞的修复能力,就会引发基因组不稳定甚至细胞死亡。靶向RS的药物即以此为机制杀伤肿瘤细胞。最近有研究发现,靶向RS能够协同免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)增强对肿瘤的杀伤作用,但其机制尚未完全阐明。该篇综述重点回顾了靶向复制应激与免疫检查点抑制剂联合治疗肿瘤的研究进展,为开发更高效的肿瘤治疗策略提供了理论依据。更多还原

【Abstract】 RS(replication stress) refers to the slowing down, stopping or collapsing of DNA replication forks due to various factors, which will activate the cellular replication stress response to cope with the replication stress. However, if the replication stress exceeds the cell’s ability to repair itself, genomic instability or even cell death will be triggered. Drugs targeting RS kill tumor cells by this mechanism. Recently, it has been found that targeting RS can synergize with ICIs(immune checkpoint inhibitors) to enhance tumor killing, but the mechanism has not been fully elucidated. This review focuses on reviewing the research progress of combining targeted replicative stress with immune checkpoint inhibitors for the treatment of tumors to provide a theoretical basis for the development of more efficient tumor treatment strategies.更多还原