填补PARP抑制剂诱导的合成致死率的空白

IF 2.6 Q3 ONCOLOGY

Molecular and Cellular Oncology Pub Date : 2021-11-02 DOI:10.1080/23723556.2021.2010512

Mariana Paes Dias, J. Jonkers

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引用次数: 4

摘要

乳腺癌1型易感蛋白(BRCA1)缺失的肿瘤是同源重组(HR)缺陷和对聚(adp -核糖)聚合酶抑制剂(PARPi)过敏的肿瘤。然而，这些肿瘤可能通过失去DNA双链断裂的末端保护而恢复HR并获得PARPi抗性。我们发现，核DNA连接酶III的缺失通过暴露复制后单链DNA (ssDNA)缺口，使hr修复的brca1缺陷细胞对PARPi重新敏感。我们和其他人的研究发现，ssDNA缺口是PARPi反应的关键决定因素。

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Filling in the gaps in PARP inhibitor-induced synthetic lethality

ABSTRACT Tumors with loss of breast cancer type 1 susceptibility protein (BRCA1) are homologous recombination (HR) deficient and hypersensitive to poly(ADP-ribose) polymerase inhibitors (PARPi). However, these tumors may restore HR and acquire PARPi resistance via loss of end-protection of DNA double-strand breaks. We found that loss of nuclear DNA ligase III resensitizes HR-restored BRCA1-deficient cells to PARPi by exposing post-replicative single-stranded DNA (ssDNA) gaps. Our work, and that of others, identifies ssDNA gaps as a key determinant of PARPi response.

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来源期刊

Molecular and Cellular Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research

CiteScore

3.20

自引率

0.00%

发文量

期刊介绍： For a long time, solid neoplasms have been viewed as relatively homogeneous entities composed for the most part of malignant cells. It is now clear that tumors are highly heterogeneous structures that evolve in the context of intimate interactions between cancer cells and endothelial, stromal as well as immune cells. During the past few years, experimental and clinical oncologists have witnessed several conceptual transitions of this type. Molecular and Cellular Oncology (MCO) emerges within this conceptual framework as a high-profile forum for the publication of fundamental, translational and clinical research on cancer. The scope of MCO is broad. Submissions dealing with all aspects of oncogenesis, tumor progression and response to therapy will be welcome, irrespective of whether they focus on solid or hematological neoplasms. MCO has gathered leading scientists with expertise in multiple areas of cancer research and other fields of investigation to constitute a large, interdisciplinary, Editorial Board that will ensure the quality of articles accepted for publication. MCO will publish Original Research Articles, Brief Reports, Reviews, Short Reviews, Commentaries, Author Views (auto-commentaries) and Meeting Reports dealing with all aspects of cancer research.