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.

中文翻译：

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应激诱导的诱变：对癌症和耐药性的影响。

基因组不稳定性是许多癌症的基础，并产生遗传变异，从而驱动癌症的发生，发展和治疗耐药性。与经典假设相反，突变纯粹以恒定，渐进的速率随机发生，微生物，植物，果蝇和人类癌细胞具有受压力反应上调的诱变机制。它们会产生短暂的遗传多样性爆发，从而促进进化，特别是当细胞对环境的适应性差时（即在受到压力时）。我们审查了从细菌到癌症，并由饥饿，药物，缺氧和其他应激源激活的应激反应依赖性（应激诱导）诱变的分子机制。我们讨论在大肠杆菌中诱变的DNA断裂修复，作为癌症机制的模型。应激反应和基因组空间限制引起的诱变在时间上的调控是整个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。我们讨论了针对靶向诱变和其他变异产生剂的可能的抗进化药物，可用于延缓癌症进展和治疗耐药性的发展。