Natural Selection in Cancer Biology: From Molecular Snowflakes to Trait Hallmarks

Abstract

Evolution by natural selection is the conceptual foundation for nearly every branch of biology and increasingly also for biomedicine and medical research. In cancer biology, evolution explains how populations of cells in tumors change over time. It is a fundamental question whether this evolutionary process is driven primarily by natural selection and adaptation or by other evolutionary processes such as founder effects and drift. In cancer biology, as in organismal evolutionary biology, there is controversy about this question and also about the use of adaptation through natural selection as a guiding framework for research. In this review, we discuss the differences and similarities between evolution among somatic cells versus evolution among organisms. We review what is known about the parameters and rate of evolution in neoplasms, as well as evidence for adaptation. We conclude that adaptation is a useful framework that accurately explains the defining characteristics of cancer. Further, convergent evolution through natural selection provides the only satisfying explanation both for how a group of diverse pathologies have enough in common to usefully share the descriptive label of “cancer” and for why this convergent condition becomes life-threatening.

Elevatedde novofatty acid biosynthesis gene expression promotes melanoma cell survival and drug resistance

“…Cancers frequently exhibit reprogrammed metabolic traits such as elevated DNFA 3 that act to sustain active proliferation and cell survival under adverse conditions, and support the process of tumorigenesis and metastasis, as well as resistance to targeted therapies. The diverse genetic paths cancers take to achieve such traits have frustrated efforts to exploit them clinically [73][74][75] .…”

Evolution of Cancer Progression in the Context of Darwinism

“…Genetically altered cells critically require complicated interactions with their surrounding microenvironment. These direct or indirect interactions generate positive/negative selection pressures applied to cancer cells with new mutations (35) (Figure 2). Such a permissive microenvironment must support the growth of genetically altered cancer cells, including cancer-initiating cells with stem cell properties.…”

New insights into the role of intra-tumor genetic heterogeneity in carcinogenesis: identification of complex single gene variance within tumors

“…We believe this confusion is partly because of a failure to investigate the nature and degree of genetic heterogeneity within single genes, a condition that we have labelled, complex single gene variance (CSGV), as opposed to just identifying mutations in different cancer-associated genes. Why this is important is that as natural selection is being increasingly identified as a critical process in cancer biology [12] , there needs to be a better understanding of the nature of the genetic variation that is being subjected to selection.…”