Poly(ADP‐ribose) polymerase‐1 (PARP‐1) plays a central role in numerous cellular processes including DNA repair, replication, and transcription. PARP interacts directly, indirectly or via PARylation with various oncogenic proteins and regulates several transcription factors thereby modulating carcinogenesis. Therapeutic inhibition of PARP is therefore perceived as a promising anticancer strategy and a number of PARP inhibitors (PARPi) are currently under development and clinical evaluation. PARPi inhibit the DNA repair pathway and thus form the concept of synthetic lethality in cancer therapeutics. Preclinical and clinical studies have shown the potential of PARPi as chemopotentiator, radiosensitizer, or as adjuvant therapeutic agents. Recent studies have shown that PARP‐1 could be either oncogenic or tumor suppressive in different cancers. PARP inhibitor resistance is also a growing concern in the clinical setting. Recently, changes in the levels of PARP‐1 activity or expression in cancer patients have provided the basis for consideration of PARP‐1 regulatory proteins as potential biomarkers. This review focuses on the current developments related to the role of PARP in cancer progression, therapeutic strategies targeting PARP‐associated oncogenic signaling, and future opportunities in use of PARPi in anticancer therapeutics.

中文翻译：

---

聚（ADP-核糖）聚合酶-1（PARP1）在癌症中的治疗靶向：当前进展，治疗策略和未来的机会。

聚（ADP-核糖）聚合酶-1（PARP-1）在许多细胞过程中起着核心作用，包括DNA修复，复制和转录。PARP与各种致癌蛋白直接，间接或通过PARylation相互作用，并调节多种转录因子，从而调节致癌作用。因此，PARP的治疗抑制被认为是一种有前途的抗癌策略，目前正在开发和临床评估许多PARP抑制剂（PARPi）。PARPi抑制DNA修复途径，因此形成了癌症治疗剂中合成杀伤力的概念。临床前和临床研究表明PARPi作为化学增效剂，放射增敏剂或辅助治疗剂的潜力。最近的研究表明，PARP-1在不同的癌症中可能具有致癌性或抑癌性。在临床环境中，PARP抑制剂的耐药性也日益引起人们的关注。最近，癌症患者中PARP-1活性或表达水平的变化为考虑将PARP-1调节蛋白作为潜在的生物标志物提供了基础。这篇综述重点关注与PARP在癌症进展中的作用有关的最新进展，针对PARP相关致癌信号的治疗策略以及在抗癌治疗中使用PARPi的未来机会。