利用复制间隙进行癌症治疗。
Exploiting replication gaps for cancer therapy.
机构信息
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
出版信息
Mol Cell. 2022 Jul 7;82(13):2363-2369. doi: 10.1016/j.molcel.2022.04.023. Epub 2022 May 13.
Abstract
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.
摘要
人们认为，DNA 双链断裂修复缺陷会使 BRCA1 或 BRCA2（BRCA）突变型肿瘤对 PARP 抑制剂（PARPi）具有选择性敏感性。但具有挑战性的是，BRCA 和 PARP1 在滞后链上的 DNA 合成中具有共同功能。因此，BRCA 缺陷或“BRCA 样”可能反映了一种固有的滞后链问题，这种问题容易受到 PARPi 等也靶向滞后链的药物的影响，这种组合会导致复制间隙的毒性积累。
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