Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Drug Discov Today. 2022 Sep;27(9):2603-2613. doi: 10.1016/j.drudis.2022.06.009. Epub 2022 Jun 24.
Drug resistance to chemotherapy and molecularly targeted therapies is a current challenge in cancer treatments. The underlying mechanisms of resistance to cytotoxic chemotherapeutics and to drugs that target a specific molecule are not understood completely. In recent years, emerging evidence has frequently suggested that the dysregulation of deubiquitinating enzymes (DUBs) plays important roles in the development of drug resistance. We focus on the molecular mechanisms through which DUBs enable cancer cells to escape cell death and survive when exposed to a variety of anti-cancer drugs. Furthermore, this review summarizes the potential application of DUB inhibitors in combination therapies to overcome drug resistance.
化疗和分子靶向治疗的耐药性是癌症治疗中的一个当前挑战。对于细胞毒性化疗药物和针对特定分子的药物的耐药性的潜在机制尚未完全了解。近年来,新出现的证据经常表明,去泛素化酶(DUBs)的失调在耐药性的发展中发挥重要作用。我们专注于 DUBs 使癌细胞在暴露于各种抗癌药物时逃避细胞死亡并存活的分子机制。此外,本综述总结了 DUB 抑制剂在联合治疗中克服耐药性的潜在应用。