A potential synthetic lethal strategy with PARP inhibitors:perspective on 'Inactivation of the tumor suppressor p53 by long noncoding RNA RMRP'

• 作者: Qian Hao Hua Lu Xiang Zhou
• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2021,（9）
• 所属期刊栏目: Research Advances
• 页码范围: 690-692
• 页数: 3页
• 语种: 英文
• DOI: 10.1093/jmcb/mjab049

摘要

The tumor suppressor p53 plays an important role in the inhibition of cancer progression,particularly in response to chemotherapy or target-specific therapy.Inactivation or mutation of p53 often becomes a cancer's tactic for drug resis-tance.One of the clinically applied ther-apeutic strategies is to inhibit poly(ADP-ribose) polymerase (PARP) activity,as PARP inhibitors are widely used for sub-sets of tumors with homologous recom-bination deficiency due to mutation of BRCA1/2 or other DNA repair-associated genes.It has been shown that p53 defi-ciency or mutation enhances the cytotox-icity of PARP inhibition in various tumors(Williamson et al.,2012).A possible mechanism underlying this is that loss of p53 impairs DNA repair path-ways,creating additional tumor vulnera-bility to PARP inhibition,as wild-type(wt) p53 transcriptionally induces the expression of genes involved in DNA repair (Vousden and Prives,2009).