Defects in DNA double-strand break repair are thought to render BRCA1 or BRCA2 (BRCA) mutant tumors selectively sensitive to PARP inhibitors (PARPis). Challenging this framework, BRCA and PARP1 share functions in DNA synthesis on the lagging strand. Thus, BRCA deficiency or “BRCAness” could reflect an inherent lagging strand problem that is vulnerable to drugs such as PARPi that also target the lagging strand, a combination that generates a toxic accumulation of replication gaps.

中文翻译：

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利用复制间隙进行癌症治疗

DNA 双链断裂修复缺陷被认为会使BRCA1或BRCA2 ( BRCA ) 突变肿瘤选择性地对 PARP 抑制剂 (PARPis) 敏感。BRCA 和 PARP1 在落后链上的 DNA 合成中共享功能，这对这一框架提出了挑战。因此，BRCA 缺陷或“BRCAness”可能反映了固有的滞后链问题，该问题容易受到 PARPi 等药物的影响，这些药物也针对滞后链，这种组合会产生复制间隙的有毒积累。