Purpose

In this paper, we provide an overview of a life history theory and how it applies to cancer evolution.

Recent findings

We review the literature on trade-offs in tumors, focusing on the trade-offs among cellular proliferation, survival, and motility. Trade-offs are critical natural constraints for almost all evolutionary processes. Many ecological studies show that trade-offs among these cellular functions maintain a genetic diversity. In addition, these trade-offs are not fixed, but rather can shift depending on the ecological circumstances in the microenvironment. This can lead to selection for the cellular capacity to respond to these differing microenvironments in ways that promote the fitness of the cancer cell. We relate these life history trade-offs to the recently developed Evo-Eco indexes and discuss how life history theory can help refine our measures of tumor evolution and ecology.

Summary

Life history theory provides a framework for understanding how the spatial and temporal variability in the tumor microenvironment-in particular resources and threats-affect trade-offs among cell survival, cell proliferation, and cell migration. We discuss how these trade-offs can potentially be leveraged in cancer therapy to increase the effectiveness of treatment.

Cancer has deep evolutionary roots and is an important source of selective pressure in organismal evolution. Yet, we find a great deal of variation in cancer vulnerabilities across the tree of life. Comparative oncology offers insights into why some species vary in their susceptibility to cancer and the mechanisms responsible for the diversity of cancer defenses. Here we provide an overview for why cancer persists across the tree of life. We then summarize current data on cancer in mammals, reptiles, and birds in comparison with commonly reported human cancers. We report on both novel and shared mechanisms of cancer protection in animals. Cross-discipline collaborations, including zoological and aquarium institutions, wildlife and evolutionary biologists, veterinarians, medical doctors, cancer biologists, and oncologists, will be essential for progress in the field of comparative oncology. Improving medical treatment of humans and animals with cancer is the ultimate promise of comparative oncology.

The presence of fetal cells has been associated with both positive and negative effects on maternal health. These paradoxical effects may be due to the fact that maternal and offspring fitness interests are aligned in certain domains and conflicting in others, which may have led to the evolution of fetal microchimeric phenotypes that can manipulate maternal tissues. We use cooperation and conflict theory to generate testable predictions about domains in which fetal microchimerism may enhance maternal health and those in which it may be detrimental. This framework suggests that fetal cells may function both to contribute to maternal somatic maintenance (e.g. wound healing) and to manipulate maternal physiology to enhance resource transmission to offspring (e.g. enhancing milk production). In this review, we use an evolutionary framework to make testable predictions about the role of fetal microchimerism in lactation, thyroid function, autoimmune disease, cancer and maternal emotional, and psychological health. Also watch the Video Abstract.

Across the tree of life, female animals share biological characteristics that place them at risk for similar diseases and disorders. Greater awareness of these shared vulnerabilities can accelerate insight and innovation in women's health. We present a broadly comparative approach to female health that can inform issues ranging from mammary, ovarian, and endometrial cancer to preeclampsia, osteoporosis, and infertility. Our focus on female health highlights the interdependence of human, animal, and environmental health. As the boundaries between human and animal environments become blurred, female animals across species are exposed to increasingly similar environmental hazards. As such, the health of female animals has unprecedented relevance to the field of woman's health. Expanding surveillance of animal populations beyond zoonoses to include noncommunicable diseases can strengthen women's health prevention efforts as environmental factors are increasingly implicated in human mortality. The physiology of nonhuman females can also spark innovation in women's health. There is growing interest in those species of which the females appear to have a level of resistance to pathologies that claim millions of human lives every year. These physiologic adaptations highlight the importance of biodiversity to human health. Insights at the intersection of women's health and planetary health can be a rich source of innovations benefitting the health of all animals across the tree of life.

Somatic evolution during cancer progression and therapy results in tumour cells that show a wide range of phenotypes, which include rapid proliferation and quiescence. Evolutionary life history theory may help us to understand the diversity of these phenotypes. Fast life history organisms reproduce rapidly, whereas those with slow life histories show less fecundity and invest more resources in survival. Life history theory also provides an evolutionary framework for phenotypic plasticity, which has potential implications for understanding 'cancer stem cells'. Life history theory suggests that different therapy dosing schedules might select for fast or slow life history cell phenotypes, with important clinical consequences.

The factors influencing cancer susceptibility and why it varies across species are major open questions in the field of cancer biology. One underexplored source of variation in cancer susceptibility may arise from trade-offs between reproductive competitiveness (e.g. sexually selected traits, earlier reproduction and higher fertility) and cancer defence. We build a model that contrasts the probabilistic onset of cancer with other, extrinsic causes of mortality and use it to predict that intense reproductive competition will lower cancer defences and increase cancer incidence. We explore the trade-off between cancer defences and intraspecific competition across different extrinsic mortality conditions and different levels of trade-off intensity, and find the largest effect of competition on cancer in species where low extrinsic mortality combines with strong trade-offs. In such species, selection to delay cancer and selection to outcompete conspecifics are both strong, and the latter conflicts with the former. We discuss evidence for the assumed trade-off between reproductive competitiveness and cancer susceptibility. Sexually selected traits such as ornaments or large body size require high levels of cell proliferation and appear to be associated with greater cancer susceptibility. Similar associations exist for female traits such as continuous egg-laying in domestic hens and earlier reproductive maturity. Trade-offs between reproduction and cancer defences may be instantiated by a variety of mechanisms, including higher levels of growth factors and hormones, less efficient cell-cycle control and less DNA repair, or simply a larger number of cell divisions (relevant when reproductive success requires large body size or rapid reproductive cycles). These mechanisms can affect intra- and interspecific variation in cancer susceptibility arising from rapid cell proliferation during reproductive maturation, intrasexual competition and reproduction.

Biologists have taken the concept of organism largely for granted. However, advances in the study of chimerism, symbiosis, bacterial-eukaryote associations, and microbial behavior have prompted a redefinition of organisms as biological entities exhibiting low conflict and high cooperation among their parts. This expanded view identifies organisms in evolutionary time. However, the ecological processes, mechanisms, and traits that drive the formation of organisms remain poorly understood. Recognizing that organismality can be context dependent, we advocate elucidating the ecological contexts under which entities do or do not act as organisms. Here we develop a "contextual organismality" framework and provide examples of entities, such as honey bee colonies, tumors, and bacterial swarms, that can act as organisms under specific life history, resource, or other ecological circumstances. We suggest that context dependence may be a stepping stone to the development of increased organismal unification, as the most integrated biological entities generally show little context dependence. Recognizing that organismality is contextual can identify common patterns and testable hypotheses across different entities. The contextual organismality framework can illuminate timeless as well as pressing issues in biology, including topics as disparate as cancer emergence, genomic conflict, evolution of symbiosis, and the role of the microbiota in impacting host phenotype.

Whole-genome analyses of human medulloblastomas show that the dominant clone at relapse is present as a rare subclone at primary diagnosis.