Group phenotypic composition in cancer

Abstract

Although individual cancer cells are generally considered the Darwinian units of selection in malignant populations, they frequently act as members of groups where fitness of the group cannot be reduced to the average fitness of individual group members. A growing body of studies reveals limitations of reductionist approaches to explaining biological and clinical observations. For example, induction of angiogenesis, inhibition of the immune system, and niche engineering through environmental acidification and/or remodeling of extracellular matrix cannot be achieved by single tumor cells and require collective actions of groups of cells. Success or failure of such group activities depends on the phenotypic makeup of the individual group members. Conversely, these group activities affect the fitness of individual members of the group, ultimately affecting the composition of the group. This phenomenon, where phenotypic makeup of individual group members impacts the fitness of both members and groups, has been captured in the term ‘group phenotypic composition’ (GPC). We provide examples where considerations of GPC could help in understanding the evolution and clinical progression of cancers and argue that use of the GPC framework can facilitate new insights into cancer biology and assist with the development of new therapeutic strategies.

Bridging Tumorigenesis and Therapy Resistance With a Non-Darwinian and Non-Lamarckian Mechanism of Adaptive Evolution

“…This prediction matches the increasingly acknowledged role of gene loss for evolutionary adaptation (115)(116)(117)(118)(119)(120)(121)(122). It also provides a plausible explanation for recurrent mutations in cancer cells (see below), recurring intratumoral phenotypic clusters (77,123,124), and the convergence towards the relatively few hallmarks of cancer (125). Importantly, most if not all the evidence presented above is commonly interpreted as, and may indeed be, the result of positive selection.…”

“…For example, it should help integrate ubiquitous and wellestablished phenomena such as pleiotropy, plasticity, and trade-offs (76). Also, it should be explicit about the relative contribution of evolutionary forces in the onset of adaptations as well as the interaction between these forces and the environment [e.g., surrounding tumor cells (77)]. Further, it should be able to integrate genetics and epigenetics, both of which play a central role in the emergence of cancer and cancer drug resistance [e.g., (13)].…”

Landscape of Epithelial Mesenchymal Plasticity as an emergent property of coordinated teams in regulatory networks

“…Here we see teams in terms of intracellular regulatory networks, but this framework of identifying composition of two (or more) groups acting together to reinforce each other in scenarios of competing outcome can be applied more broadly. For instance different cells in a microenvironment can form groups with pro tumor and anti-tumor inflence (41). How and when are these teams of cells formed remains to be identified.…”

Invasion front dynamics of interactive populations in environments with barriers

“…More importantly, tumor cells that push the healthy tissue belong to different clones 17 . These subpopulations may cooperate 18 – 21 or compete 22 – 24 with each other during their way to invade the surrounding healthy tissue 25 . Despite huge literature on clonal diversity in tumors, it is not clear that how such interactions regulate invasion and how the intensity of environmental barriers restricts invasion.…”