Genetic complexity and DNA damage repair defects are common in different cancer types and can induce tumor-specific vulnerabilities. Poly(ADP-ribose) polymerase (PARP) inhibitors exploit defects in the DNA repair pathway through synthetic lethality and have emerged as promising anticancer therapies, especially in tumors harboring deleterious germline or somatic breast cancer susceptibility gene (BRCA) mutations. However, the utility of PARP inhibitors could be expanded beyond germline BRCA1/2 mutated cancers by causing DNA damage with cytotoxic agents in the presence of a DNA repair inhibitor. US Food and Drug Administration (FDA)-approved PARP inhibitors include olaparib, rucaparib, and niraparib, while veliparib is in the late stage of clinical development. Talazoparib inhibits PARP catalytic activity, trapping PARP1/2 on damaged DNA, and it has been approved by the US FDA for the treatment of metastatic germline BRCA1/2 mutated breast cancers in October 2018. The talazoparib side effect profile more closely resembles traditional chemotherapeutics rather than other clinically approved PARP inhibitors. In this review, we discuss the scientific evidence that has emerged from both experimental and clinical studies in the development of talazoparib. Future directions will include optimizing combination therapy with chemotherapy, immunotherapies and targeted therapies, and in developing and validating biomarkers for patient selection and stratification, particularly in malignancies with ‘BRCAness’.

遗传复杂性和DNA损伤修复缺陷在不同类型的癌症中很常见，并且可以诱发特定于肿瘤的脆弱性。聚（ADP-核糖）聚合酶（PARP）抑制剂可通过合成杀伤力利用DNA修复途径中的缺陷，并已成为有前途的抗癌疗法，尤其是在携带有害种系或体细胞乳腺癌易感性基因（BRCA）突变的肿瘤中。但是，PARP抑制剂的用途可以扩展到种系BRCA1 / 2之外。通过在DNA修复抑制剂的存在下用细胞毒性剂引起DNA损伤来突变癌症。美国食品药品监督管理局（FDA）批准的PARP抑制剂包括olaparib，rucaparib和niraparib，而veliparib处于临床开发的后期。塔拉唑帕尼抑制PARP催化活性，将PARP1 / 2捕获在受损的DNA上，并且已被美国FDA批准用于治疗转移性生殖系BRCA1 / 2。在2018年10月突变了乳腺癌。他唑帕尼的副作用与传统化学疗法更像是化学疗法，而不是其他临床认可的PARP抑制剂。在这篇综述中，我们讨论了在他拉唑帕尼的开发中来自实验和临床研究的科学证据。未来的方向将包括优化与化学疗法，免疫疗法和靶向疗法的联合治疗，以及开发和验证用于患者选择和分层的生物标志物，特别是在具有“ BRCAness”特征的恶性肿瘤中。