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Development of poly(ADP-ribose) polymerase inhibitor and immunotherapy combinations: progress, pitfalls, and promises
Trends in Cancer ( IF 14.3 ) Pub Date : 2021-06-19 , DOI: 10.1016/j.trecan.2021.05.004
Melissa M Pham 1 , Natalie Y L Ngoi 2 , Guang Peng 3 , David S P Tan 4 , Timothy A Yap 5
Affiliation  

The efficacy of poly(ADP-ribose) polymerase inhibitors (PARPi) is restricted by inevitable drug resistance, while their use in combination with chemotherapy and targeted agents is commonly associated with dose-limiting toxicities. Immune checkpoint blockade (ICB) has demonstrated durable responses in different solid tumors and is well-established across multiple cancers. Despite this, single agent activity is limited to a minority of patients and drug resistance remains an issue. Building on the monotherapy success of both drug classes, combining PARPi with ICB may be a safe and well-tolerated strategy with the potential to improve survival outcomes. In this review, we present the preclinical, translational, and clinical data supporting the combination of DNA damage response (DDR) and ICB as well as consider important questions to be addressed with future research.



中文翻译:

聚(ADP-核糖)聚合酶抑制剂和免疫疗法组合的开发:进展、陷阱和前景

聚(ADP-核糖)聚合酶抑制剂(PARPi)的功效受到不可避免的耐药性的限制,而它们与化疗和靶向药物联合使用通常与剂量限制性毒性有关。免疫检查点阻断(ICB)已在不同实体瘤中表现出持久的反应,并且在多种癌症中得到了广泛应用。尽管如此,单药活性仅限于少数患者,耐药性仍然是一个问题。基于两类药物单药治疗的成功,PARPi 与 ICB 相结合可能是一种安全且耐受性良好的策略,有可能改善生存结果。在这篇综述中,我们提出了支持 DNA 损伤反应 (DDR) 和 ICB 结合的临床前、转化和临床数据,并考虑了未来研究需要解决的重要问题。

更新日期:2021-06-19
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