Journal
ANNUAL REVIEW OF GENETICS, VOL 48
Volume 48, Issue -, Pages 215-236Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-genet-120213-092314
Keywords
genome instability; drug resistance; precision medicine; cancer evolution; intratumor heterogeneity
Categories
Funding
- MRC [G0902275] Funding Source: UKRI
- Cancer Research UK [17786, 16459] Funding Source: researchfish
- Medical Research Council [G0902275] Funding Source: researchfish
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Subclonal cancer populations change spatially and temporally during the disease course. Studies are revealing branched evolutionary cancer growth with low-frequency driver events present in subpopulations of cells, providing escape mechanisms for targeted therapeutic approaches. Despite such complexity, evidence is emerging for parallel evolution of subclones, mediated through distinct somatic events converging on the same gene, signal transduction pathway, or protein complex in different subclones within the same tumor. Tumors may follow gradualist paths (microevolution) as well as major shifts in evolutionary trajectories (macroevolution). Although macroevolution has been subject to considerable controversy in post-Darwinian evolutionary theory, we review evidence that such nongradual, saltatory leaps, driven through chromosomal rearrangements or genome doubling, may be particularly relevant to tumor evolution. Adapting cancer care to the challenges imposed by tumor micro- and macroevolution and developing deeper insight into parallel evolutionary events may prove central to improving outcome and reducing drug development costs.
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