Adaptive Evolution: How Bacteria and Cancer Cells Survive Stressful Conditions and Drug Treatment

Abstract

Summary: Cancer is characterized by loss of the regulatory mechanisms that preserve homeostasis in multicellular organisms, such as controlled proliferation, cell–cell adhesion, and tissue differentiation. The breakdown of multicellularity rules is accompanied by activation of “selfish,” unicellular-like life features, which are linked to the increased adaptability to environmental changes displayed by cancer cells. Mechanisms of stress response, resembling those observed in unicellular organisms, are actively exploited by mammalian cancer cells to boost genetic diversity and increase chances of survival under unfavorable conditions, such as lack of oxygen/nutrients or exposure to drugs. Unicellular organisms under stressful conditions (e.g., antibiotic treatment) stop replicating or slowly divide and transiently increase their mutation rates to foster diversity, a process known as adaptive mutability. Analogously, tumor cells exposed to drugs enter a persister phenotype and can reduce DNA replication fidelity, which in turn fosters genetic diversity. The implications of adaptive evolution are of relevance to understand resistance to anticancer therapies.

Pan-cancer surveys indicate cell cycle-related roles of primate-specific genes in tumors and embryonic cerebrum

“…On the one hand, Darwinian medicine has championed the idea that disease susceptibility is predisposed by macroevolutionary history [ 1 , 3 , 4 , 91 ]. Accordingly, studies of atavism and antagonistic pleiotropy provide clues for understanding tumor biology [ 22 , 28 , 33 ]. Herein, by building upon previous efforts [ 19 – 24 ], our meta-analyses across 13 cancer types demonstrated that the pan-cancer upregulation of UC genes involved in basic cellular machinery tends to promote tumor (Figs.…”

“…Phylostratigraphic or gene age analyses provide abundant supporting evidence: (1) cancer-related genes often emerge in unicellular (UC) ancestors or early metazoan (EM) ancestors [19][20][21][22]; (2) UC genes tend to be upregulated in tumors, while EM genes are often downregulated [23,24]. Therefore, atavism is increasingly accepted as a theoretical framework to understand cancer [4,[25][26][27] and adaptive mutability enabled by the ancient memory is even proposed as a target in tumor therapy [22,28]. On the other hand, natural selection may maximize the fitness in youth at the cost of promoting diseases of aging [3,29,30].…”

Turnover shapes evolution of birth and death rates

“…Recently, even mutational processes have been linked to be at least partly modulated by the environment, as more evidence of adaptive mutability has been accumulated in unicellular and cancer cell populations [12, 13]. Epigenetic inheritance, phenotypic plasticity and other strictly non-genetic mechanisms which can create phenotypic diversity subject to selection further confound eco-evolutionary dynamics [14], thus calling for integration rather than separation of ecology and evolution.…”

Clinical utility of PDX cohorts to reveal biomarkers of intrinsic resistance and clonal architecture changes underlying acquired resistance to cetuximab in HNSCC

“…63 Resistance to therapy could be innate or acquired. 64 Multiple studies have demonstrated the importance of clonal diversity and dynamics in resistance to therapeutic agents, 65 and the use of model systems like PTCs can be extremely useful in supporting clonal expansion studies about the process of acquired resistance. 46 Consider that in a typical clinical setting, large-scale molecular profiling of a patient's tumor can only be conducted for a few time points, i.e., when the tumor is surgically removed or when a biopsy is taken.…”