Evolutionary Processes in Cancer

Cancer develops through the evolution of somatic cells in multicellular bodies. The familiar dynamics of organismal evolution, including mutations, natural selection, genetic drift, and migration, also occur among the cells of multicellular organisms. In some cases, but not all, these evolutionary processes lead to cancer. This has profound implications for both our understanding of cancer and our treatment of the disease, as well as its prevention. All of our medical interventions impose selective pressures on the heterogeneous populations of billions of cells in tumors, and tend to select for mutant cells that are resistant to the intervention, regardless of whether the intervention is a drug, radiation, the immune system, or anything else that has been tried. We will likely need evolutionary and ecological approaches to cancer to manage its evolution in response to our interventions. The field of the evolutionary biology and ecology of cancer is still young and relatively small. We are in the early stages of translating ideas and tools from evolutionary biology and ecology to study and manage cancers. There is a desperate need for more researchers with expertise in evolutionary biology and ecology to apply their skills and ideas to cancer. Currently, there are far more important questions that need to be addressed than there are people to address them.

2021 ◽  
pp. 99-118
Author(s):  
Franklin M. Harold

The story of life tells of relentless expansion from obscure beginnings to smother the earth in organized biochemistry. First came the prokaryotes, Bacteria and Archaea, followed some two billion years later by eukaryotic microbes. The latter pattern of organization underpins the rise of multicellular organisms, and their spectacular proliferation over the past 600 million years. There have been no fundamentally new kinds of organisms since, but the rise of mind culminating in humanity may signal a new phase in life’s history. Life has expanded in both quantity and quality, a gyre of mounting size, complexity, and functional capacity; in some elusive sense evolution is progressive. Multicellularity, the key invention, is not singular but happened multiple times in several eukaryotic lineages. The proliferation of higher organisms was probably enabled by increased energy flow, and dependent on the increase in atmospheric oxygen. It is studded with innovations in structure, physiology, and behavior, whose origin is a recurrent theme in evolutionary biology. Novelty is rooted in mutational events at the gene level, supplemented by the acquisition of genes from the outside by both gene transfer and symbiosis, and possibly by other avenues. Chance events were scrutinized and culled by natural selection. There appears to be no intrinsic progressive drive, but natural selection generally favors the more functional and better organized.


2017 ◽  
Vol 4 (10) ◽  
pp. 170470 ◽  
Author(s):  
Marta Bertolaso ◽  
Anna Maria Dieli

The major transitions approach in evolutionary biology has shown that the intercellular cooperation that characterizes multicellular organisms would never have emerged without some kind of multilevel selection. Relying on this view, the Evolutionary Somatic view of cancer considers cancer as a breakdown of intercellular cooperation and as a loss of the balance between selection processes that take place at different levels of organization (particularly single cell and individual organism). This seems an elegant unifying framework for healthy organism, carcinogenesis, tumour proliferation, metastasis and other phenomena such as ageing. However, the gene-centric version of Darwinian evolution, which is often adopted in cancer research, runs into empirical problems: proto-tumoural and tumoural features in precancerous cells that would undergo ‘natural selection’ have proved hard to demonstrate; cells are radically context-dependent, and some stages of cancer are poorly related to genetic change. Recent perspectives propose that breakdown of intercellular cooperation could depend on ‘fields’ and other higher-level phenomena, and could be even mutations independent. Indeed, the field would be the context, allowing (or preventing) genetic mutations to undergo an intra-organism process analogous to natural selection. The complexities surrounding somatic evolution call for integration between multiple incomplete frameworks for interpreting intercellular cooperation and its pathologies.


2017 ◽  
Vol 284 (1866) ◽  
pp. 20171164 ◽  
Author(s):  
Michael Briga ◽  
Robert M. Griffin ◽  
Vérane Berger ◽  
Jenni E. Pettay ◽  
Virpi Lummaa

Many fundamental concepts in evolutionary biology were discovered using non-human study systems. Humans are poorly suited to key study designs used to advance this field, and are subject to cultural, technological, and medical influences often considered to restrict the pertinence of human studies to other species and general contexts. Whether studies using current and recent human populations provide insights that have broader biological relevance in evolutionary biology is, therefore, frequently questioned. We first surveyed researchers in evolutionary biology and related fields on their opinions regarding whether studies on contemporary humans can advance evolutionary biology. Almost all 442 participants agreed that humans still evolve, but fewer agreed that this occurs through natural selection. Most agreed that human studies made valuable contributions to evolutionary biology, although those less exposed to human studies expressed more negative views. With a series of examples, we discuss strengths and limitations of evolutionary studies on contemporary humans. These show that human studies provide fundamental insights into evolutionary processes, improve understanding of the biology of many other species, and will make valuable contributions to evolutionary biology in the future.


Paleobiology ◽  
2006 ◽  
Vol 32 (4) ◽  
pp. 562-577 ◽  
Author(s):  
Michael A. Bell ◽  
Matthew P. Travis ◽  
D. Max Blouw

Inferring the causes for change in the fossil record has been a persistent problem in evolutionary biology. Three independent lines of evidence indicate that a lineage of the fossil stickleback fish Gasterosteus doryssus experienced directional natural selection for reduction of armor. Nonetheless, application to this lineage of three methods to infer natural selection in the fossil record could not exclude random process as the cause for armor change. Excluding stabilizing selection and genetic drift as the mechanisms for biostratigraphic patterns in the fossil record when directional natural selection was the actual cause is very difficult. Biostratigraphic sequences with extremely fine temporal resolution among samples and other favorable properties must be used to infer directional selection in the fossil record.


2018 ◽  
Author(s):  
Stephan Peischl ◽  
Kimberly J. Gilbert

AbstractUnderstanding the causes and consequences of range expansions or range shifts has a long history in evolutionary biology. Recent theoretical, experimental, and empirical work has identified two particularly interesting phenomena in the context of species range expansions: (i) gene surfing and the relaxation of natural selection, and (ii) spatial sorting. The former can lead to an accumulation of deleterious mutations at range edges, causing an expansion load and slowing down expansion. The latter can create gradients in dispersal-related traits along the expansion axis and cause an acceleration of expansion. We present a theoretical framework that treats spatial sorting and gene surfing as spatial versions of natural selection and genetic drift, respectively. This model allows us to study analytically how gene surfing and spatial sorting interact, and to derive the probability of fixation of pleiotropic mutations at the expansion front. We use our results to predict the co-evolution of mean fitness and dispersal rates, taking into account the effects of random genetic drift, natural selection and spatial sorting, as well as correlations between fitnessand dispersal-related traits. We identify a “rescue effect” of spatial sorting, where the evolution of higher dispersal rates at the leading edge rescues the population from incurring expansion load.


Author(s):  
Daniel B. Thompson

The environmental variables hypothesized to cause behavioral adaptation are distributed across a wide array of spatial scales, from local variation in factors such as food sources and territorial encounters to regional or continental variation in factors such as seasonality and the presence of predators. Geographic variation in behavior, the topic of this book, is just one of the potential evolutionary responses to environmental variation. Because behavioral divergence among populations generated by disparate natural selection can be counterbalanced by the homogenizing influence of gene flow, adaptive geographic variation can evolve only if the spatial scale of variation in natural selection is greater than the scale of gene flow (Endler 1977, Slatkin 1978). If geographic variation does not evolve because the spatial scale of selection is smaller than the scale of gene flow, populations may instead evolve adaptive phenotypic plasticity (Bradshaw 1965); the expression, by a single genotype, of different fitness-enhancing phenotypes in different environments. Because the same evolutionary processes operating on different spatial scales can generate behavioral geographic variation, behavioral phenotypic plasticity, or geographic variation in phenotypic plasticity, I devote this chapter to development of a hierarchical perspective tor studying environmental variation and behavioral evolution. This perspective emphasizes the shared evolutionary processes and research methodologies common to different levels of spatial variation, such as the balance of gene flow, natural selection, and genetic drift, the relationship between environmental patch size and local adaptation, and the effects of historical contingencies and genetic constraints on behavioral adaptation and phenotypic plasticity. In what follows, I review behavioral research in two unrelated taxa to illustrate the range of possible evolutionary responses to different patterns of environmental variation. First, I discuss different spatial scales of adaptation in the climbing behavior of deer mice (Peromyscus maniculatus) and provide a hierarchical analysis of the effects of natural selection, genetic drift, and gene flow. Second, I discuss diet-induced phenotypic plasticity in the feeding behavior of acridid grasshoppers (Melanoplus femurrubrum and M. sanguinipes) and the evolution of behavioral norms of reaction in response to local spatial and temporal variation in plant environments.


Author(s):  
Timothy G. Barraclough

‘Species’ are central to understanding the origin and dynamics of biological diversity; explaining why lineages split into multiple distinct species is one of the main goals of evolutionary biology. However, the existence of species is often taken for granted, and precisely what is meant by species and whether they really exist as a pattern of nature has rarely been modelled or critically tested. This novel book presents a synthetic overview of the evolutionary biology of species, describing what species are, how they form, the consequences of species boundaries and diversity for evolution, and patterns of species accumulation over time. The central thesis is that species represent more than just a unit of taxonomy; they are a model of how diversity is structured as well as how groups of related organisms evolve. The author adopts an intentionally broad approach to consider what species constitute, both theoretically and empirically, and how we detect them, drawing on a wealth of examples from microbes to multicellular organisms.


2021 ◽  
Vol 22 (12) ◽  
pp. 6492
Author(s):  
Paola Giussani ◽  
Alessandro Prinetti ◽  
Cristina Tringali

Immunotherapy is now considered an innovative and strong strategy to beat metastatic, drug-resistant, or relapsing tumours. It is based on the manipulation of several mechanisms involved in the complex interplay between cancer cells and immune system that culminates in a form of immune-tolerance of tumour cells, favouring their expansion. Current immunotherapies are devoted enforcing the immune response against cancer cells and are represented by approaches employing vaccines, monoclonal antibodies, interleukins, checkpoint inhibitors, and chimeric antigen receptor (CAR)-T cells. Despite the undoubted potency of these treatments in some malignancies, many issues are being investigated to amplify the potential of application and to avoid side effects. In this review, we discuss how sphingolipids are involved in interactions between cancer cells and the immune system and how knowledge in this topic could be employed to enhance the efficacy of different immunotherapy approaches. In particular, we explore the following aspects: how sphingolipids are pivotal components of plasma membranes and could modulate the functionality of surface receptors expressed also by immune cells and thus their functionality; how sphingolipids are related to the release of bioactive mediators, sphingosine 1-phosphate, and ceramide that could significantly affect lymphocyte egress and migration toward the tumour milieu, in addition regulating key pathways needed to activate immune cells; given the renowned capability of altering sphingolipid expression and metabolism shown by cancer cells, how it is possible to employ sphingolipids as antigen targets.


2006 ◽  
Vol 26 (14) ◽  
pp. 5249-5258 ◽  
Author(s):  
Vincenzo Coppola ◽  
Colleen A. Barrick ◽  
Sara Bobisse ◽  
Maria Cecilia Rodriguez-Galan ◽  
Michela Pivetta ◽  
...  

ABSTRACT Trafficking and cell adhesion are key properties of cells of the immune system. However, the molecular pathways that control these cellular behaviors are still poorly understood. Cybr is a scaffold protein highly expressed in the hematopoietic/immune system whose physiological role is still unknown. In vitro studies have shown it regulates LFA-1, a crucial molecule in lymphocyte attachment and migration. Cybr also binds cytohesin-1, a guanine nucleotide exchange factor for the ARF GTPases, which affects actin cytoskeleton remodeling during cell migration. Here we show that expression of Cybr in vivo is differentially modulated by type 1 cytokines during lymphocyte maturation. In mice, Cybr deficiency negatively affects leukocytes circulating in blood and lymphocytes present in the lymph nodes. Moreover, in a Th1-polarized mouse model, lymphocyte trafficking is impaired by loss of Cybr, and Cybr-deficient mice with aseptic peritonitis have fewer cells than controls present in the peritoneal cavity, as well as fewer leukocytes leaving the bloodstream. Mutant mice injected with Moloney murine sarcoma/leukemia virus develop significantly larger tumors than wild-type mice and have reduced lymph node enlargement, suggesting reduced cytotoxic T-lymphocyte migration. Taken together, these data support a role for Cybr in leukocyte trafficking, especially in response to proinflammatory cytokines in stress conditions.


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