对肿瘤生物学认识的进步揭示了癌症发生和进展的标志，其中包括失调的 DNA 损伤修复 (DDR) 机制。利用潜在的肿瘤基因组不稳定性和 DDR 中的肿瘤特异性缺陷，聚 (ADP-核糖) 聚合酶 (PARP) 抑制剂 (PARPi) 诱导的 DNA 损伤成为一种新型的非化疗治疗机会。 PARPis 目前已获批用于多种肿瘤类型，其中在同源重组修复 (HRR) 缺陷的肿瘤中获益最大，包括 BRCA1/2 基因 (BRCA) 以及 PALB2 和 Rad51c 等其他通路成员的种系和体细胞突变。文章总结了当前的批准情况以及已知和提议的 PARPi 耐药机制。此外，还讨论了克服 PARPi 耐药性的治疗策略，包括正在进行的临床试验。PARPi 已被证明是一种安全有效的疗法，代表了多种实体瘤类型的基石治疗。阐明先天性和获得性耐药机制，再加上利用 PARPi 活性并预防或逆转获得性耐药性的新型治疗方案的出现，为进一步扩大 PARPi 在癌症治疗中的作用提供了机会。

Advances in understanding of tumor biology shed light on hallmarks of cancer development and progression that include dysregulated DNA damage repair (DDR) machinery. Leveraging underlying tumor genomic instability and tumor specific defects in DDR, Poly (ADP-ribose) polymerases (PARP) inhibitors (PARPi) induced DNA damage emerges as a novel non-chemotherapy therapeutic opportunity. PARPis are currently approved in multiple tumor types, with the largest benefit seen in tumors with homologous recombination repair (HRR) deficiency, including germline and somatic mutations in BRCA1/2 genes (BRCA) and other pathway members such as PALB2 and Rad51c.This review article summarizes the current approval landscape and known and proposed mechanisms of resistance to PARPi. Further, therapeutic strategies to overcome PARPi resistance are discussed, including ongoing clinical trials.PARPi have proven to be a safe and effective therapy and represent a cornerstone treatment across multiple solid tumor types. Elucidating innate and acquired mechanisms of resistance, coupled with the emergence of novel therapeutic options to capitalize on the activity of PARPi and prevent or reverse the acquisition of resistance, provides an opportunity to further expand the role of PARPi in cancer therapy.