Ecology and Evolution of Cancer 1st Edition
Editors: Beata Ujvari, Benjamin Roche, and Frederic Thomas. Academic Press 2017
eBook ISBN: 9780128043806 Paperback ISBN: 9780128043103
Book Commentary by Leonard Nunney, UC Riverside, Department of Biology
Cancer defines a broad set of potentially lethal diseases occurring when our own cells turn against us. Although cancer is not a single disease, we can raise the question of whether there are broad unifying principles that would allow us to understand the similarities, and, perhaps especially, the differences among cancers. Understandably, most cancer research is not directed at elucidating unifying principles, instead focusing on topics such as the mechanistic details of the initiation and development of specific cancers, and of a tumor’s interaction with the immune system. This approach has been very effective at unraveling the specifics of “how” events unfold, but can do little to help us understand the “why” of cancer. It can be argued that understanding “why” requires a much broader perspective, one that integrates the evolutionary and ecological context into cancer biology, an argument detailed in the recent edited volume “Ecology and Evolution of Cancer”.
Even simple differences among cancers cannot easily be understood within a purely mechanistic paradigm. For example, viewed at the individual level, it is clear that cancer is generally a disease of old age, but the increase is not uniform, with some cancers increasing much more than others. Furthermore, some forms of cancer are not diseases of old age but of childhood. Variation is also found in causation. While some cancers can be linked to inherited mutations or environmental insults, most cancers have no clear causation. Similarly, there is variation in the genetic basis of cancer suppression. It is clear that cancers are closely linked to the abnormal functioning of certain genes or gene networks, however there is not a single “cancer-prevention” network, and the specific genes or networks involved vary among cancer types, a pattern that is understandable only in an evolutionary context. Furthermore, these same generalities apply to other well studied mammals such as mice and domestic dogs but scaled to their life span, so that the cancer risk of an 1.5 year old mouse is similar to the risk of a proportionately aged human of around 70 years old. It is easy to overlook the importance of this shift from absolute time to relative time, a shift that illustrates the central role of adaptive evolution responding to life history and ecology in regulating the onset of cancer. Similarly, at the cellular level evolution also plays a central role. Once a cancer has progressed far enough to be detected, some cancers are rapidly lethal while others progress slowly. Some cancers respond well to chemotherapy, while others may respond initially but then recur. But at the other end of the spectrum, it has long been known that in some exceptional cases a cancer will spontaneously disappear without treatment.
To place these generalities within a broad conceptual framework, it is necessary to dig into the biological context of cancer. Cancer suppression has a long evolutionary history stretching back more than 600 million years to the origins of complex multicellular animals, when the conflicts between individual organisms and the individual cells that they consisted of had to be resolved; however, that same evolutionary conflict continues today, driving genetic differences among species due to their life history and ecological differences. Fortunately for us, this 600 million year old evolutionary conflict favors the individual organism, but at the micro-evolutionary scale, the tables are turned and, once a cancer has initiated, the real-time eco-evolutionary dynamics favor the spread of cancer clones.
Building a general framework for understanding cancer is long overdue. However, the process has started and already suggests novel avenues of research. For example, the importance of a comparative approach is increasingly being recognized, based on the realization that cancer suppression is an evolving trait that adapts organisms to changes in body size and longevity. This realization has focused attention on mechanisms of cancer suppression that have evolved in very large and/or long-lived species, raising the very real possibility that these mechanisms may be of therapeutic value to humans. At the level of a developing cancer, advances in genomic sequencing have made evolutionary-based phylogenetic analyses of cell lineages possible, allowing for the application of evolutionary theory developed to minimize the onset of resistance to chemotherapy.
An important step towards a general framework for understanding cancer is represented by the array of ideas presented in the “Ecology and Evolution of Cancer”. It provides strong arguments for recognizing the importance of integrating ecology and evolution into our understanding of why cancer occurs and why it is so difficult to prevent – arguably an important step that will be invaluable in helping cancer biologists find a robust solution to the problem of cancer.
Introduction: Five Evolutionary Principles for Understanding Cancer
Chapter 1 – The Evolutionary Origins of Cancer and of Its Control by Immune Policing and Genetic Suppression
Chapter 2 – Cancer Prevalence and Etiology in Wild and Captive Animals
Chapter 3 – Infection and Cancer in Nature
Chapter 4 – Pseudohypoxia: Life at the Edge
Chapter 5 – The Genomic Landscape of Cancers
Chapter 6 – The Epigenetic Component in Cancer Evolution
Chapter 7 – Evolution of Cancer Defense Mechanisms Across Species
Chapter 8 – Coevolution of Tumor Cells and Their Microenvironment: “Niche Construction in Cancer”
Chapter 9 – Evolutionary Perspective of Tumorigenesis and Antitumor Immunity: A Comparative Approach
Chapter 10 – The Response of Cancer Cell Populations to Therapies
Chapter 11 – Ecology of the Metastatic Process
Chapter 12 – Transmissible Cancer: The Evolution of Interindividual Metastasis
Chapter 13 – Cancer in Animals: Reciprocal Feedbacks Between Evolution of Cancer Resistance and Ecosystem Functioning
Chapter 14 – Applying Tools From Evolutionary Biology to Cancer Research