Petos Paradox And The Evolution Of Cancer Suppression
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Peto's Paradox and the Evolution of Cancer Suppression
| Author | : Brian Michael Muir |
| Publisher | : |
| Total Pages | : 177 |
| Release | : 2016 |
| Genre | : African elephant |
| ISBN | : 9781369300901 |
An unsuspected finding in cancer research is that different cancers result from mutations in different genes. If cancer is a problem of multicellularity, why is there not a single set of genes regulating all cancers of multicellular animals? Cancer risk is expected to be higher in larger, longer-lived species since the risk of cancer-initiating somatic mutations is expected to increase with the number of lifetime cell divisions. However, this expected relationship is not observed, and has been termed Peto's Paradox. The evolution of additional mechanisms of cancer suppression in large, long-lived species can resolve the paradox and may explain the differences in the genetics of cancer between species and tissues. In a proof-of-concept experimental evolution study fruit flies with hereditary tumors were selected to evolve suppression of these tumors. A significant reduction in the incidence of tumors was observed in the final populations. The genetic changes involved in the evolution of additional mechanisms may come in two forms. First, a cancer-suppression mechanism acting may be recruited by its upregulation of gene expression in the target tissue. To address this, I compared the levels of gene expression of 15 tumor suppressor genes and 8 proto-oncogenes across dozens of non- diseased human tissues. I found that 15 of the 23 genes have their highest level of expression in the tissue types where they are implicated in hereditary cancer, relative to the tissue types where they are not. Second, additional mechanisms may arise by duplications of pre-existing tumor suppressor genes already acting in the target tissue. The recent finding of additional copies of the critical tumor suppressor gene, TP53, in the large-bodied African Elephant and the long-lived microbats has been suggested to explain the low-rates of cancers in these species. However, in a phylogenetic comparison of the coding regions of these retrogene copies relative to the normal TP53 copies in 24 mammals, I find that the additional copies in the elephant and bats are truncated early by stop codons, and are poorly conserved. In conclusion, incorporating evolutionary theory into cancer biology is critical for understanding the variation in cancer genetics across tissues and species.
Ecology and Evolution of Cancer
| Author | : Beata Ujvari |
| Publisher | : Academic Press |
| Total Pages | : 292 |
| Release | : 2017-02-08 |
| Genre | : Medical |
| ISBN | : 0128043806 |
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. This work engages the expertise of a multidisciplinary research team to collate and review the latest knowledge and developments in this exciting research field. The evolutionary perspective of cancer has gained significant international recognition and interest, which is fully understandable given that somatic cellular selection and evolution are elegant explanations for carcinogenesis. Cancer is now generally accepted to be an evolutionary and ecological process with complex interactions between tumor cells and their environment sharing many similarities with organismal evolution. As a critical contribution to this field of research the book is important and relevant for the applications of evolutionary biology to understand the origin of cancers, to control neoplastic progression, and to prevent therapeutic failures. Covers all aspects of the evolution of cancer, appealing to researchers seeking to understand its origins and effects of treatments on its progression, as well as to lecturers in evolutionary medicine Functions as both an introduction to cancer and evolution and a review of the current research on this burgeoning, exciting field, presented by an international group of leading editors and contributors Improves understanding of the origin and the evolution of cancer, aiding efforts to determine how this disease interferes with biotic interactions that govern ecosystems Highlights research that intends to apply evolutionary principles to help predict emergence and metastatic progression with the aim of improving therapies
Natural Selection in the Wild. (MPB-21), Volume 21
| Author | : John A. Endler |
| Publisher | : Princeton University Press |
| Total Pages | : 352 |
| Release | : 2020-03-31 |
| Genre | : Science |
| ISBN | : 0691209510 |
Natural selection is an immense and important subject, yet there have been few attempts to summarize its effects on natural populations, and fewer still which discuss the problems of working with natural selection in the wild. These are the purposes of John Endler's book. In it, he discusses the methods and problems involved in the demonstration and measurement of natural selection, presents the critical evidence for its existence, and places it in an evolutionary perspective. Professor Endler finds that there are a remarkable number of direct demonstrations of selection in a wide variety of animals and plants. The distribution of observed magnitudes of selection in natural populations is surprisingly broad, and it overlaps extensively the range of values found in artificial selection. He argues that the common assumption that selection is usually weak in natural populations is no longer tenable, but that natural selection is only one component of the process of evolution; natural selection can explain the change of frequencies of variants, but not their origins.
Cancer Evolution
| Author | : Charles Swanton |
| Publisher | : Perspectives Cshl |
| Total Pages | : 350 |
| Release | : 2017 |
| Genre | : Medical |
| ISBN | : 9781621821434 |
Tumor progression is driven by mutations that confer growth advantages to different subpopulations of cancer cells. As a tumor grows, these subpopulations expand, accumulate new mutations, and are subjected to selective pressures from the environment, including anticancer interventions. This process, termed clonal evolution, can lead to the emergence of therapy-resistant tumors and poses a major challenge for cancer eradication efforts. Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine examines cancer progression as an evolutionary process and explores how this way of looking at cancer may lead to more effective strategies for managing and treating it. The contributors review efforts to characterize the subclonal architecture and dynamics of tumors, understand the roles of chromosomal instability, driver mutations, and mutation order, and determine how cancer cells respond to selective pressures imposed by anticancer agents, immune cells, and other components of the tumor microenvironment. They compare cancer evolution to organismal evolution and describe how ecological theories and mathematical models are being used to understand the complex dynamics between a tumor and its microenvironment during cancer progression. The authors also discuss improved methods to monitor tumor evolution (e.g., liquid biopsies) and the development of more effective strategies for managing and treating cancers (e.g., immunotherapies). This volume will therefore serve as a vital reference for all cancer biologists as well as anyone seeking to improve clinical outcomes for patients with cancer.
Oxford Textbook of Cancer Biology
| Author | : Francesco Pezzella |
| Publisher | : Oxford University Press |
| Total Pages | : 505 |
| Release | : 2019-05-02 |
| Genre | : Medical |
| ISBN | : 0198779453 |
The study of the biology of tumours has grown to become markedly interdisciplinary, involving chemists, statisticians, epidemiologists, mathematicians, bioinformaticians, and computer scientists alongside biologists, geneticists, and clinicians. The Oxford Textbook of Cancer Biology brings together the most up-to-date developments from different branches of research into one coherent volume, providing a comprehensive and current account of this rapidly evolving field. Structured in eight sections, the book starts with a review of the development and biology of multi-cellular organisms, how they maintain a healthy homeostasis in an individual, and a description of the molecular basis of cancer development. The book then illustrates, as once cells become neoplastic, their signalling network is altered and pathological behaviour follows. It explores the changes that cancer cells can induce in nearby normal tissue, the new relationship established between them and the stroma, and the interaction between the immune system and tumour growth. The authors illustrate the contribution provided by high throughput techniques to map cancer at different levels, from genomic sequencing to cellular metabolic functions, and how information technology, with its vast amounts of data, is integrated with traditional cell biology to provide a global view of the disease. The effect of the different types of treatments on the biology of the neoplastic cells are explored to understand on the one side, why some treatments succeed, and on the other, how they can affect the biology of resistant and recurrent disease. The book concludes by summarizing what we know to date about cancer, and in what direction our understanding of cancer is moving. Edited by leading authorities in the field with an international team of contributors, this book is an essential resource for scholars and professionals working in the wide variety of sub-disciplines that make up today's cancer research and treatment community. It is written not only for consultation, but also for easy cover-to-cover reading.
The Cheating Cell
| Author | : Athena Aktipis |
| Publisher | : Princeton University Press |
| Total Pages | : 256 |
| Release | : 2020-03-24 |
| Genre | : Medical |
| ISBN | : 0691163847 |
A fundamental and groundbreaking reassessment of how we view and manage cancer When we think of the forces driving cancer, we don’t necessarily think of evolution. But evolution and cancer are closely linked because the historical processes that created life also created cancer. The Cheating Cell delves into this extraordinary relationship, and shows that by understanding cancer’s evolutionary origins, researchers can come up with more effective, revolutionary treatments. Athena Aktipis goes back billions of years to explore when unicellular forms became multicellular organisms. Within these bodies of cooperating cells, cheating ones arose, overusing resources and replicating out of control, giving rise to cancer. Aktipis illustrates how evolution has paved the way for cancer’s ubiquity, and why it will exist as long as multicellular life does. Even so, she argues, this doesn’t mean we should give up on treating cancer—in fact, evolutionary approaches offer new and promising options for the disease’s prevention and treatments that aim at long-term management rather than simple eradication. Looking across species—from sponges and cacti to dogs and elephants—we are discovering new mechanisms of tumor suppression and the many ways that multicellular life-forms have evolved to keep cancer under control. By accepting that cancer is a part of our biological past, present, and future—and that we cannot win a war against evolution—treatments can become smarter, more strategic, and more humane. Unifying the latest research from biology, ecology, medicine, and social science, The Cheating Cell challenges us to rethink cancer’s fundamental nature and our relationship to it.
Adaptive Oncogenesis
| Author | : James DeGregori |
| Publisher | : Harvard University Press |
| Total Pages | : 289 |
| Release | : 2018-03-09 |
| Genre | : Science |
| ISBN | : 0674545397 |
Popular understanding holds that genetic changes create cancer. James DeGregori uses evolutionary principles to propose a new way of thinking about cancerÕs occurrence. Cancer is as much a disease of evolution as it is of mutation, one in which mutated cells outcompete healthy cells in the ecosystem of the bodyÕs tissues. His theory ties cancerÕs progression, or lack thereof, to evolved strategies to maximize reproductive success. Through natural selection, humans evolved genetic programs to maintain bodily health for as long as necessary to increase the odds of passing on our genesÑbut not much longer. These mechanisms engender a tissue environment that favors normal stem cells over precancerous ones. Healthy tissues thwart cancer cellsÕ ability to outcompete their precancerous rivals. But as our tissues age or accumulate damage from exposures such as smoking, normal stem cells find themselves less optimized to their ecosystem. Cancer-causing mutations can now help cells adapt to these altered tissue environments, and thus outcompete normal cells. Just as changes in a speciesÕ habitat favor the evolution of new species, changes in tissue environments favor the growth of cancerous cells. DeGregoriÕs perspective goes far in explaining who gets cancer, when it appears, and why. While we cannot avoid mutations, it may be possible to sustain our tissuesÕ natural and effective system of defense, even in the face of aging or harmful exposures. For those interested in learning how cancers arise within the human body, the insights in Adaptive Oncogenesis offer a compelling perspective.
The Extraordinary Biology of the Naked Mole-Rat
| Author | : Rochelle Buffenstein |
| Publisher | : Springer Nature |
| Total Pages | : 450 |
| Release | : 2021-08-23 |
| Genre | : Medical |
| ISBN | : 3030659437 |
This volume focuses on the huge advances in the last 25 years on the use of this animal model for biomedical research (cancer, heart disease and neurodegeneration), fundamental neuroscience and basic subterranean biology. In 2013, Science magazine named the naked mole-rat as the Vertebrate of the Year. This was partly due to research carried out documenting its extreme longevity, negligible senescence, and prolonged maintenance of cancer free, good health well into old age as well as seminal work on mechanisms involved in these processes, pain and hypoxia resistance. In addition to this research focus on longevity and chronic diseases such as cancer and cardiovascular disease, the naked mole-rat has also made a substantial contribution to the fields of ecophysiology, neuroscience and behavior. With international contributions, this book provides a valuable text for zoological students, behavioral scientists and biomedical researchers.
The Emperor of All Maladies
| Author | : Siddhartha Mukherjee |
| Publisher | : Simon and Schuster |
| Total Pages | : 624 |
| Release | : 2011-08-09 |
| Genre | : Health & Fitness |
| ISBN | : 1439170916 |
Winner of the Pulitzer Prize and a documentary from Ken Burns on PBS, this New York Times bestseller is “an extraordinary achievement” (The New Yorker)—a magnificent, profoundly humane “biography” of cancer—from its first documented appearances thousands of years ago through the epic battles in the twentieth century to cure, control, and conquer it to a radical new understanding of its essence. Physician, researcher, and award-winning science writer, Siddhartha Mukherjee examines cancer with a cellular biologist’s precision, a historian’s perspective, and a biographer’s passion. The result is an astonishingly lucid and eloquent chronicle of a disease humans have lived with—and perished from—for more than five thousand years. The story of cancer is a story of human ingenuity, resilience, and perseverance, but also of hubris, paternalism, and misperception. Mukherjee recounts centuries of discoveries, setbacks, victories, and deaths, told through the eyes of his predecessors and peers, training their wits against an infinitely resourceful adversary that, just three decades ago, was thought to be easily vanquished in an all-out “war against cancer.” The book reads like a literary thriller with cancer as the protagonist. Riveting, urgent, and surprising, The Emperor of All Maladies provides a fascinating glimpse into the future of cancer treatments. It is an illuminating book that provides hope and clarity to those seeking to demystify cancer.
