Brutovský Branislav
Department of Biophysics, Faculty of Science, P. J. Šafárik University, Jesenná 5, 041 54 Košice, Slovakia.
Cancers (Basel). 2022 Jul 1;14(13):3253. doi: 10.3390/cancers14133253.
The exploitation of the evolutionary modus operandi of cancer to steer its progression towards drug sensitive cancer cells is a challenging research topic. Integrating evolutionary principles into cancer therapy requires properly identified selection level, the relevant timescale, and the respective fitness of the principal selection unit on that timescale. Interpretation of some features of cancer progression, such as increased heterogeneity of isogenic cancer cells, is difficult from the most straightforward evolutionary view with the cancer cell as the principal selection unit. In the paper, the relation between the two levels of intratumour heterogeneity, genetic, due to genetic instability, and non-genetic, due to phenotypic plasticity, is reviewed and the evolutionary role of the latter is outlined. In analogy to the evolutionary optimization in a changing environment, the cell state dynamics in cancer clones are interpreted as the risk diversifying strategy bet hedging, optimizing the balance between the exploitation and exploration of the cell state space.
利用癌症的进化运作方式，引导其向对药物敏感的癌细胞发展，是一个具有挑战性的研究课题。将进化原理整合到癌症治疗中，需要正确识别选择水平、相关时间尺度以及该时间尺度上主要选择单元的各自适应性。从以癌细胞为主要选择单元的最直接进化观点来看，很难解释癌症进展的一些特征，比如同基因癌细胞异质性增加。本文回顾了肿瘤内两种异质性水平之间的关系，即由于基因不稳定导致的遗传异质性和由于表型可塑性导致的非遗传异质性，并概述了后者的进化作用。类似于在变化环境中的进化优化，癌症克隆中的细胞状态动态被解释为风险多样化策略——套期保值，优化细胞状态空间利用与探索之间的平衡。
