Cancer as an evolutionary and ecological process pdf

Since anthropogenic perturbations drastically increase cancer rates in wild populations of animals, deciphering the complex interactions between senescence and cancer now constitutes a key challenge in. This is in part due to our relentless desire to view the world through a simplifier glass and in part due to the technical. Application of evolutionary principles to cancer therapy. Jan 01, 2003 the origin of cancer can be likened to the process that leads either to speciation or to the adaptation of individuals to a certain environment see below for a distinction, except that the selection process involves cells, not individuals. I believe it definitely is an evolutionary process. Within a neoplasm, a mosaic of mutant cells compete for space and resources, evade predation by the immune. Here, we apply evolutionary and ecological theory to understand the transition from benign sedentary cells to invasive. During this process, evolving cancer cell populations encounter restrictive ecological niches within the body, such as the primary tumor, circulatory system, and diverse metastatic sites.

Classifying the evolutionary and ecological features of neoplasms. The dynamic cancer ecosystem, with its rich temporal and spatial diversity in environmental conditions and heritable cell phenotypes, is remarkably robust to therapeutic perturbations. Jun 24, 2019 cancer is a leading cause of death in human populations and has recently been shown to be more prevalent across species than previously thought. Nov 30, 2015 cancer is best understood in our view from a multilevel perspective, as both a byproduct of selection at other levels of organization, and as subject to selection and drift at several levels of organization. The ecology of breast cancer is an heroic summary of an extremely complex body of science. The evolutionary approach to cancer has been the dominant theory of cancer since it was proposed in the 1970s and has continued to be developed as a unifying theory for understanding the emergence and progression of cancers.

Cancers can be described as open complex adaptive systems. Classifying the evolutionary and ecological features of. The evolution and ecology of resistance in cancer therapy. Pdf cancer as an evolutionary and ecological process john. These mechanisms were initially necessary for the evolution of multicellular organisms and became even more important as. We must follow the science, embrace the complexity of breast cancer, and recognize the promising insights that the ecological paradigm of breast cancer offers. Cancer development can be viewed as an evolutionary and ecological process, in which the tumour microenvironment tme is likely to play a. Armitage and doll explained the cancer incidence data, as a function of age, as a process of the sequential accumulation of somatic mutations or. Turning ecology and evolution against cancer memorial sloan. Cancer cells utilize resources and construct habitats within the tissues of the body just as organisms do in the natural world. Based on a consensus conference of experts in the evolution and ecology of cancer, this article proposes a framework for classifying tumours that includes four evolutionary and ecological. Cancer is a disease of clonal evolution within the body 1,2,3.

We expand on this idea, drawing upon multilevel selection theory. Accumulating evidence suggests that intratumor heterogeneity likely is the key to understanding treatment failure. Our understanding of cancer is being transformed by exploring clonal diversity, drug resistance, and causation within an evolutionary framework. Feb 24, 2016 recently, the traditional maximum dose density paradigm has been questioned 9, 10 on the basis of a theoretical model that views cancer therapy as an evolutionary and ecological process. Mar 05, 20 glioblastoma gb is the most common and aggressive primary brain malignancy, with poor prognosis and a lack of effective therapeutic options. Cancer evolutionary genomics and modelling laboratory, centre for evolution and cancer, the institute of cancer research, sutton, uk.

Exploiting evolutionary principles to prolong tumor control. Evolutionary determinants of cancer cancer discovery. Although evolution of resistance remains the proximate. Tumorigenesis has been described as an evolutionary process decades ago 1, 2, but still very few molecular studies have even attempted to analyze tumor progression from a population biology point of view. However, cancer is more than just an evolutionary process. First, cancer cells coopt signaling pathways that are otherwise adaptive at the organismic level. Nov 16, 2006 cancer is a disease of clonal evolution within the body 1,2,3. We 6, and others 4,5, have proposed that a unifying analytical framework can be found in evolutionary theory. Sep 22, 2015 however, cancer is more than just an evolutionary process. Cancer is best understood in our view from a multilevel perspective, as both a byproduct of selection at other levels of organization, and as subject to selection and drift at several levels of organization. This represents a central ecological and evolutionary problem in treating cancers. Although the idea of cancer as an evolutionary problem is not new 1,4, historically, little attention has been focused. Mar 16, 2020 this represents a central ecological and evolutionary problem in treating cancers.

Cancer as an evolutionary and ecological process lauren m. Early mathematical modeling of cancer, by armitage and doll, set the stage for the future development of the somatic evolutionary theory of cancer. Intratumor heterogeneity in human glioblastoma reflects. A summary of the links between evolution and cancer from howard hughes medical institute. Cancer is a dead end whether or not it kills its host, whereas. Pdf cancer as an evolutionary and ecological process. How cancer shapes evolution, and how evolution shapes cancer. This kind of evolutionary ecological analysis of variations in different organs may prove of great value in cancer prevention and treatment. Cancer as an evolutionary and ecological process sites at usc.

Behavioral ecological principles explain competition and cooperation among cancer clones. The ecology of breast cancer collaborative on health and. Open because they freely communicate with their surroundings, complex because they contain multiple components, and adaptive because each element can change over time and interact with other components in complicated, often nonlinear, ways. Measuring cancer evolution from the genome graham 2017. Unfortunately, the tme is largely ignored or considered static in most cancer evolution models, and different cancers are often studied in isolation. Recently, the traditional maximum dose density paradigm has been questioned 9, 10 on the basis of a theoretical model that views cancer therapy as an evolutionary and ecological process. The therapeutic resilience of advanced cancer is a consequence of its character as a complex, dynamic, and adaptive ecosystem engendering robustness, underpinned by genetic diversity and epigenetic plasticity. An ecological measure of immunecancer colocalization as a. Ecological principles explain how cancers interact with microenvironments. Cancer as an evolutionary and ecological process nature. Even when response to therapy is clinically complete, adaptive tumor strategies almost inevitably emerge and the tumor returns.

This single cell acquires a first mutation that makes it a little bit more like a cancer cell. Jul 21, 2015 the recognition of cancer as a somatic evolutionary process requiring multiple rounds of selection for adaptive oncogenic mutations has armed cancer modeling with parametric approaches and led to the foundation of the current multistage model of carcinogenesis operating with mutation fitness effects as the pivotal element of the theory. An evolutionary approach can unite and explain the many avenues of cancer research by allowing us to see cancer as an ecosystem, concluded dr. Adaptive therapy using models and measures of the past and present state of the individual patients cancer to anticipate and steer the ecological and evolutionary dynamics of the disease by adjusting the time course of therapy accordingly.

Future studies taking an evolutionaryecological perspective could uncover novel adaptations of cancer cells, and elucidate the tradeoffs under which they evolve. Although evolution of resistance remains the proximate cause of death in most. Recent advances in cancer research have shown that tumours, like species striving for survival. People started realizing this in 1970s, in a couple of papers published back then. Here we examine cancer through the lens of evolutio nary and ecological biology. Species evolve by mutation and selection acting on individuals in a population. An evolutionary approach can help us understand why cancer exists and how it progresses somatic evolution, how cancer cells interact with environments ecological approaches, why it is not more common natural selection for cancer suppression mechanisms, and why cancer suppression mechanisms can never be perfect constraints, trade. Ecology and evolution of cancer is a timely work outlining ideas that not only represent a substantial and original contribution to the fields of evolution, ecology, and cancer, but also goes beyond by connecting the interfaces of these disciplines. Concepts in solid tumor evolution stanford university. We describe here how recent evolutionary ecological studies have elucidated the roles of predation by the immune system and competition among normal and cancerous cells in the somatic evolution of cancer. Future studies taking an evolutionary ecological perspective could uncover novel adaptations of cancer cells, and elucidate the tradeoffs under which they evolve. Evolutionary dynamics of carcinogenesis and why targeted. Cancer is a leading cause of death in human populations and has recently been shown to be more prevalent across species than previously thought.

However, an alternative explanation could be that large organs e. Evolutionary foundations for cancer biology aktipis 20. Glioblastoma gb is the most common and aggressive primary brain malignancy, with poor prognosis and a lack of effective therapeutic options. Despite the broad appreciation of cancer as an evolutionary process, much less work has gone into characterizing the ecological aspects of cancer 2,3 6 2527 but see refs 2830. A general theory of adaptive cancer evolution is lacking. Among such forces, natural selection, here defined as differential cellular proliferation among distinct somatic cell genotypes, is particularly interesting because its action might be thwarted in. Cancer repeats, the tree of life does not the most obvious difference between cancer and organismal evolution is that the substrate of the former is a somatic cell, whereas the latter is a germline process. These contrast with benign tumors, which do not spread. One of the major developments in cancer research in recent years has been the construction of models that treat cancer as a cellular population subject to natural selection. Cancer as an evolutionary and ecological process arizona. There is widespread recognition of the importance of these evolutionary and ecological processes in cancer, but to date, no system has been. This alternative model rests on three major assumptions. The dynamic nature of this ecological and evolutionary process requires us to rethink treatment. Cancer is driven by the somatic evolution of cell lineages that have escaped controls on replication and by the populationlevel evolution of genes that influence cancer risk.

Cancer development within an individual is also an evolutionary process, which in many respects mirrors species evolution. Although tumorigenesis has been accepted as an evolutionary process, many forces may operate differently in cancers than in organisms, as they evolve at vastly different time scales. The recognition of cancer as a somatic evolutionary process requiring multiple rounds of selection for adaptive oncogenic mutations has armed cancer modeling with parametric approaches and led to the foundation of the current multistage model of carcinogenesis operating with mutation fitness effects as the pivotal element of the theory. Sep 15, 2017 based on a consensus conference of experts in the evolution and ecology of cancer, this article proposes a framework for classifying tumours that includes four evolutionary and ecological. Hela cells have been classified as a different organism because they have the ability to grow outside the host indefinitely and their genome is. There are two examples that i can think of, which can support this argument. An evolutionary framework for treating pediatric sarcomas. The origin of cancer can be likened to the process that leads either to speciation or to the adaptation of individuals to a certain environment see below for a distinction, except that the selection process involves cells, not individuals. Hence, we focus on how the coupling between evolu tion and ecology may affect tumour dynamics. Jan 22, 20 an evolutionary approach can unite and explain the many avenues of cancer research by allowing us to see cancer as an ecosystem, concluded dr aktipis.

Exploiting ecological principles to better understand cancer. Although cancer is conventionally defined as a disease of the genes, we propose that a teleological understanding of cancer will not necessarily emerge from cataloguing the vast number of genetic changes observed in clini cal tumours. Evolution selects for organisms that achieve homeostasis and this evolutionary process also makes them capable of recovering from environmental and genetic. Cancer is best understood in our view from a multilevel perspective, as both a byproduct of selection at other levels of organization, and as subject to. Evolutionary theories are critical for understanding cancer development at the level of species as well as at the level of cells and tissues, and for developing effective therapies. Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. Cancer as an evolutionary process at the cell level. Within a neoplasm, a mosaic of mutant cells compete for space and resources, evade predation by the immune system and can even cooperate to disperse and colonize new organs. Cancer development can be viewed as an evolutionary and ecological process, in which the tumour microenvironment tme is likely to play a critical role. Competition in the world of finches and warblers, competition within and between species is a major force in generating adaptations, structuring communities of interacting species and. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in bowel movements. Ta graham, evolution and cancer laboratory, barts cancer institute, charterhouse square, queen mary university of london, ec1m 6bq, uk.

Armitage and doll explained the cancer incidence data, as a function of age, as a process of the sequential accumulation of somatic mutations or other rate limiting steps. This has profound clinical implications for neoplastic progression, cancer prevention and cancer therapy. Cancer evolution in a changing microenvironment biorxiv. Evolutionary biology should be central to this endeavor. Animals have evolved potent tumorsuppressive mechanisms to prevent cancer development. How cancer shapes evolution and how evolution shapes cancer. First, phenotypically or environmentally mediated resistant cells are present before treatment 11.