胸部癌症包括非小细胞肺癌（NSCLC）、小细胞肺癌（SCLC）和恶性胸膜间皮瘤（MPM）。总的来说，它们是全球恶性肿瘤死亡率最高的国家。基因组不稳定性是癌症的普遍特征，它会促进突变和肿瘤进化。 DNA 损伤反应 (DDR) 基因的缺陷会加剧基因组的不稳定性。由 BRCA1/BRCA2 失活引起的同源重组缺陷 (HRD) 可用于利用聚 ADP 核糖聚合酶 (PARP) 抑制剂对乳腺癌和卵巢癌以及前列腺癌和胰腺癌进行治疗性合成致死。然而，DDR 缺乏及其在胸癌中的治疗意义尚不明确。新出现的证据表明，一部分胸部癌症可能存在 DDR 缺陷，因此可能是 DDR 药物的有效靶点。在这里，我们回顾了有关胸癌 DDR 的当前证据，并讨论了通过此类疗法实现临床获益的挑战和前景。© 2024。作者，获得 Springer Nature Switzerland AG 的独家许可。

Thoracic cancers comprise non-small cell lung cancers (NSCLCs), small cell lung cancers (SCLCs) and malignant pleural mesotheliomas (MPM). Collectively, they account for the highest rate of death from malignancy worldwide. Genomic instability is a universal feature of cancer, which fuels mutations and tumour evolution. Deficiencies in DNA damage response (DDR) genes amplify genomic instability. Homologous recombination deficiency (HRD), resulting from BRCA1/BRCA2 inactivation, is exploited for therapeutic synthetic lethality with poly-ADP ribose polymerase (PARP) inhibitors in breast and ovarian cancers, as well as in prostate and pancreatic cancers. However, DDR deficiency and its therapeutic implications are less well established in thoracic cancers. Emerging evidence suggests that a subset of thoracic cancers may harbour DDR deficiency and may, thus, be effectively targeted with DDR agents. Here, we review the current evidence surrounding DDR in thoracic cancers and discuss the challenges and promise for achieving clinical benefit with such therapeutics.© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.