DNA repair as a shared hallmark in cancer and ageing.
DNA repair as a shared hallmark in cancer and ageing.
复制标题
DOI：
10.1002/1878-0261.13285
复制
发表时间：
2022-09
影响因子：
6.6
通讯作者：
Mostoslavsky, Raul
中科院分区：
文献类型：
--
作者：
Clarke, Thomas L.;Mostoslavsky, Raul
越来越多的证据表明，DNA损伤和基因组不稳定在衰老中起着至关重要的作用。哺乳动物细胞已经发展出广泛的复杂和精心安排的DNA修复途径，以响应和解决来自外源性和内源性来源的许多不同类型的DNA损伤。这些修复途径中的缺陷会导致加速或过早衰老综合征，并增加癌症发展的可能性。了解DNA修复的基本机制将有助于开发治疗衰老相关疾病的新策略。在这里，我们重新审视DNA损伤修复的过程，以及这些过程如何导致包括衰老和癌症在内的疾病。我们还回顾了最近对DNA修复的机制见解，并讨论了如何将这些见解用于开发治疗人类疾病的新治疗策略。我们讨论了在临床上使用PARP抑制剂治疗乳腺癌和卵巢癌以及与获得性耐药相关的挑战。最后，我们讨论了DNA修复途径靶向治疗如何超越PARP抑制，寻找更创新、更有效的癌症治疗方法。在这篇综述中，我们重新审视了DNA损伤修复的过程，以及这些过程如何导致包括衰老和癌症在内的疾病。我们还回顾了最近对DNA修复的机制见解，并讨论了如何将这些见解用于开发治疗人类疾病的新治疗策略。
Increasing evidence demonstrates that DNA damage and genome instability play a crucial role in ageing. Mammalian cells have developed a wide range of complex and well‐orchestrated DNA repair pathways to respond to and resolve many different types of DNA lesions that occur from exogenous and endogenous sources. Defects in these repair pathways lead to accelerated or premature ageing syndromes and increase the likelihood of cancer development. Understanding the fundamental mechanisms of DNA repair will help develop novel strategies to treat ageing‐related diseases. Here, we revisit the processes involved in DNA damage repair and how these can contribute to diseases, including ageing and cancer. We also review recent mechanistic insights into DNA repair and discuss how these insights are being used to develop novel therapeutic strategies for treating human disease. We discuss the use of PARP inhibitors in the clinic for the treatment of breast and ovarian cancer and the challenges associated with acquired drug resistance. Finally, we discuss how DNA repair pathway‐targeted therapeutics are moving beyond PARP inhibition in the search for ever more innovative and efficacious cancer therapies. In this review, we revisit the processes involved in DNA damage repair and how these can contribute to diseases, including ageing and cancer. We also review recent mechanistic insights into DNA repair and discuss how these insights are being used to develop novel therapeutic strategies for treating human disease.
登录
查看更多内容
影响因子：
64.5
作者：
Alt FW;Zhang Y;Meng FL;Guo C;Schwer B
通讯作者：
Schwer B
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
影响因子：
3
作者：
Beher, Dirk;Wu, John;Wang, Minghan
通讯作者：
Wang, Minghan
影响因子：
3.8
作者：
Alt, Frederick W.;Schwer, Bjoern
通讯作者：
Schwer, Bjoern