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首页> 外文期刊>Seminars in cancer biology >Lethal mutagenesis: targeting the mutator phenotype in cancer.
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Lethal mutagenesis: targeting the mutator phenotype in cancer.

机译：致命诱变：针对癌症中的突变表型。

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摘要

The evolution of cancer and RNA viruses share many similarities. Both exploit high levels of genotypic diversity to enable extensive phenotypic plasticity and thereby facilitate rapid adaptation. In order to accumulate large numbers of mutations, we have proposed that cancers express a mutator phenotype. Similar to cancer cells, many viral populations, by replicating their genomes with low fidelity, carry a substantial mutational load. As high levels of mutation are potentially deleterious, the viral mutation frequency is thresholded at a level below which viral populations equilibrate in a traditional mutation-selection balance, and above which the population is no longer viable, i.e., the population undergoes an error catastrophe. Because their mutation frequencies are fine-tuned just below this error threshold, viral populations are susceptible to further increases in mutational load and, recently this phenomenon has been exploited therapeutically by a concept that has been termed lethal mutagenesis. Here we review the application of lethal mutagenesis to the treatment of HIV and discuss how lethal mutagenesis may represent a novel therapeutic approach for the treatment of solid cancers.
机译：癌症和RNA病毒的进化有许多相似之处。两者都利用高水平的基因型多样性来实现广泛的表型可塑性，从而促进快速适应。为了积累大量的突变，我们提出了癌症表达突变表型。与癌细胞相似，许多病毒种群通过低保真度复制其基因组而携带大量突变。由于高水平的突变可能有害，因此将病毒突变频率限制在一个水平，在该水平以下，病毒种群在传统的突变选择平衡中达到平衡，而在该水平之上该种群不再可行，即该种群遭受错误灾难。由于其突变频率恰好在此错误阈值以下进行了微调，因此病毒种群易受突变负荷进一步增加的影响，最近，这种现象已被称为致命诱变的概念用于治疗。在这里，我们综述了致死诱变在HIV治疗中的应用，并讨论了致死诱变如何代表固态癌症的新型治疗方法。

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