Chapter 17 - Toward an Ultimate Explanation of Intratumor Heterogeneity
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In Silico implementation of evolutionary paradigm in therapy design: Towards anti-cancer therapy as Darwinian process
2020, Journal of Theoretical BiologyCitation Excerpt :This strategy increases the long-term survival and growth of an entire lineage instead of conferring an immediate fitness benefit to one individual (Carja and Plotkin, 2017). Based on the formal similarity of evolving cancer cell population with bacteria, viruses or yeast, it has been recently proposed that the structure of intratumor heterogeneity is an evolutionary trait which evolves towards the maximum clonal fitness at the cancer-relevant timescale in changing (or uncertain) environment and that its structure corresponds to the bet-hedging strategy (Chisholm et al., 2016; Nichol et al., 2016; Gravenmier et al., 2018; Thomas et al., 2017) which has been recently put into therapeutic context (Mathis et al., 2017). Distinguishing between the intratumor heterogeneity due to the differences in the DNA sequences and that resulting from the epigenetic modifications is instructive for the biological insight as well as for the ’physical’ realization of an eventual therapy.
Toward understanding of the role of reversibility of phenotypic switching in the evolution of resistance to therapy
2018, Physics Letters, Section A: General, Atomic and Solid State PhysicsCitation Excerpt :In bacteria, the well known risk-diversification strategy evolved in the populations when facing uncertain future and/or environment [13–15] is the bet-hedging strategy [16,17,10]. Based on formal similarity of evolving cancer cells population with bacteria, viruses or yeast, it has been recently proposed that the structure of intratumor heterogeneity is evolutionary trait as well, evolving to maximize clonal fitness at a cancer-relevant timescale in changing (or uncertain) environment and that its structure corresponds to the bet-hedging strategy [18–22] which has been recently put into therapeutic context [23,24]. To sum up, the genome stays the main protagonist (i.e. selection unit) in the evolution of cancer cells, nevertheless with non-genetic heterogeneity of its eventual clone being the crucial adaptive trait at cancer-relevant, instead of proximate timescale.