Stress-Induced Mutagenesis: Implications in Cancer and Drug Resistance.
Stress-Induced Mutagenesis: Implications in Cancer and Drug Resistance.
复制标题
DOI：
10.1146/annurev-cancerbio-050216-121919
复制
发表时间：
2017-03
影响因子：
7.7
通讯作者：
Rosenberg SM
中科院分区：
文献类型：
--
作者：
Fitzgerald DM;Hastings PJ;Rosenberg SM
基因组不稳定性是许多癌症的基础，并产生遗传变异，驱动癌症的发生、进展和治疗抗性。与突变以恒定、渐进的速率纯粹随机发生的经典假设相反，微生物、植物、苍蝇和人类癌细胞具有通过应激反应上调的诱变机制。这些产生短暂的，基因多样性的爆发，可以推动进化，特别是当细胞对环境适应不良时，也就是说，当压力。我们回顾了从细菌到癌症发生的应激反应依赖性（应激诱导）诱变的分子机制，并通过饥饿，药物，缺氧和其他应激源激活。我们讨论了大肠杆菌中的致突变DNA断裂修复作为癌症机制的模型。应激反应对突变的时间调控和基因组中的空间限制是生命之树的共同主题。两者都可以加速进化，包括癌症的进化。我们讨论了可能的抗进化性药物，旨在靶向诱变和其他变异发生器，可用于延迟癌症进展和治疗耐药性的演变。
Genomic instability underlies many cancers and generates genetic variation that drives cancer initiation, progression, and therapy resistance. In contrast with classical assumptions that mutations occur purely stochastically at constant, gradual rates, microbes, plants, flies, and human cancer cells possess mechanisms of mutagenesis that are upregulated by stress responses. These generate transient, genetic-diversity bursts that can propel evolution, specifically when cells are poorly adapted to their environments—that is, when stressed. We review molecular mechanisms of stress-response-dependent (stress-induced) mutagenesis that occur from bacteria to cancer, and are activated by starvation, drugs, hypoxia, and other stressors. We discuss mutagenic DNA break repair in Escherichia coli as a model for mechanisms in cancers. The temporal regulation of mutagenesis by stress responses and spatial restriction in genomes are common themes across the tree of life. Both can accelerate evolution, including the evolution of cancers. We discuss possible anti-evolvability drugs, aimed at targeting mutagenesis and other variation generators, that could be used to delay the evolution of cancer progression and therapy resistance.
登录
查看更多内容
影响因子：
30.8
作者：
Burns, Michael B.;Temiz, Nuri A.;Harris, Reuben S.
通讯作者：
Harris, Reuben S.
基于肿瘤微环境的癌细胞杀伤的背景综合致死率。
影响因子：
11.2
作者：
Chan N;Pires IM;Bencokova Z;Coackley C;Luoto KR;Bhogal N;Lakshman M;Gottipati P;Oliver FJ;Helleday T;Hammond EM;Bristow RG
通讯作者：
Bristow RG
影响因子：
64.8
作者：
Chen, Guangbo;Bradford, William D.;Seidel, Chris W.;Li, Rong
通讯作者：
Li, Rong
影响因子：
5.3
作者：
Bindra, RS;Schaffer, PJ;Glazer, PM
通讯作者：
Glazer, PM
研究肺炎球菌类型的诱导物质转化的化学性质：通过从III型肺炎球菌分离出的脱氧核糖核酸分数诱导转化。
DOI：
10.1084/jem.79.2.137
发表时间：
1944-02-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Avery OT;Macleod CM;McCarty M
通讯作者：
McCarty M