Camille Jacqueline

Evolutionary perspective of cancer: myth, metaphors, and reality

The evolutionary perspective of cancer (which origins and dynamics result from evolutionary processes) has gained significant international recognition over the past decade and generated a wave of enthusiasm among researchers. In this context, several authors proposed that insights into evolutionary and adaptation dynamics of cancers can be gained by studying the evolutionary strategies of organisms. Although this reasoning is fundamentally correct, in our opinion, it contains a potential risk of excessive adaptationism, potentially leading to the suggestion of complex adaptations that are unlikely to evolve among cancerous cells. For example, the ability of recognizing related conspecifics and adjusting accordingly behaviors as in certain free‐living species appears unlikely in cancer. Indeed, despite their rapid evolutionary rate, malignant cells are under selective pressures for their altered lifestyle for only few decades. In addition, even though cancer cells can theoretically display highly sophisticated adaptive responses, it would be crucial to determine the frequency of their occurrence in patients with cancer, before therapeutic applications can be considered. Scientists who try to explain oncogenesis will need in the future to critically evaluate the metaphorical comparison of selective processes affecting cancerous cells with those affecting organisms. This approach seems essential for the applications of evolutionary biology to understand the origin of cancers, with prophylactic and therapeutic applications.

Cancer: an emergent property of disturbed resource‐rich environments? Ecology meets personalized medicine

For an increasing number of biologists, cancer is viewed as a dynamic system governed by evolutionary and ecological principles. Throughout most of human history, cancer was an uncommon cause of death and it is generally accepted that common components of modern culture, including increased physiological stresses and caloric intake, favor cancer development. However, the precise mechanisms for this linkage are not well understood. Here, we examine the roles of ecological and physiological disturbances and resource availability on the emergence of cancer in multicellular organisms. We argue that proliferation of ‘profiteering phenotypes’ is often an emergent property of disturbed, resource‐rich environments at all scales of biological organization. We review the evidence for this phenomenon, explore it within the context of malignancy, and discuss how this ecological framework may offer a theoretical background for novel strategies of cancer prevention. This work provides a compelling argument that the traditional separation between medicine and evolutionary ecology remains a fundamental limitation that needs to be overcome if complex processes, such as oncogenesis, are to be completely understood.

Cancer brings forward oviposition in the fly Drosophila melanogaster

Abstract Hosts often accelerate their reproductive effort in response to a parasitic infection, especially when their chances of future reproduction decrease with time from the onset of the infection. Because malignancies usually reduce survival, and hence potentially the fitness, it is expected that hosts with early cancer could have evolved to adjust their life‐history traits to maximize their immediate reproductive effort. Despite the potential importance of these plastic responses, little attention has been devoted to explore how cancers influence animal reproduction. Here, we use an experimental setup, a colony of genetically modified flies Drosophila melanogaster which develop colorectal cancer in the anterior gut, to show the role of cancer in altering life‐history traits. Specifically, we tested whether females adapt their reproductive strategy in response to harboring cancer. We found that flies with cancer reached the peak period of oviposition significantly earlier (i.e., 2 days) than healthy ones, while no difference in the length and extent of the fecundity peak was observed between the two groups of flies. Such compensatory responses to overcome the fitness‐limiting effect of cancer could explain the persistence of inherited cancer‐causing mutant alleles in the wild.

Infections and cancer: the "fifty shades of immunity" hypothesis

BackgroundSince the beginning of the twentieth century, infection has emerged as a fundamental aspect of cancer causation with a growing number of pathogens recognized as oncogenic. Meanwhile, oncolytic viruses have also attracted considerable interest as possible agents of tumor destruction.DiscussionLost in the dichotomy between oncogenic and oncolytic agents, the indirect influence of infectious organisms on carcinogenesis has been largely unexplored. We describe the various ways – from functional aspects to evolutionary considerations such as modernity mismatches – by which infectious organisms could interfere with oncogenic processes through immunity. Finally, we discuss how acknowledging these interactions might impact public health approaches and suggest new guidelines for therapeutic and preventive strategies both at individual and population levels.SummaryInfectious organisms, that are not oncogenic neither oncolytic, may play a significant role in carcinogenesis, suggesting the need to increase our knowledge about immune interactions between infections and cancer.

Host manipulation by cancer cells: Expectations, facts, and therapeutic implications

Similar to parasites, cancer cells depend on their hosts for sustenance, proliferation and reproduction, exploiting the hosts for energy and resources, and thereby impairing their health and fitness. Because of this lifestyle similarity, it is predicted that cancer cells could, like numerous parasitic organisms, evolve the capacity to manipulate the phenotype of their hosts to increase their own fitness. We claim that the extent of this phenomenon and its therapeutic implications are, however, underappreciated. Here, we review and discuss what can be regarded as cases of host manipulation in the context of cancer development and progression. We elaborate on how acknowledging the applicability of these principles can offer novel therapeutic and preventive strategies. The manipulation of host phenotype by cancer cells is one more reason to adopt a Darwinian approach in cancer research.

The importance of cancer cells for animal evolutionary ecology

Reciprocal interactions between hosts, their symbionts and their oncobiota (cancer cell communities) are yet to be studied in detail. Considering malignant cells in addition to the holobiont perspective allows greater understanding of the processes governing both host phenotypes and cancer dynamics.

Cancer: a disease at the crossroads of trade-offs

Central to evolutionary theory is the idea that living organisms face phenotypic and/or genetic trade‐offs when allocating resources to competing life‐history demands, such as growth, survival, and reproduction. These trade‐offs are increasingly considered to be crucial to further our understanding of cancer. First, evidences suggest that neoplastic cells, as any living entities subject to natural selection, are governed by trade‐offs such as between survival and proliferation. Second, selection might also have shaped trade‐offs at the organismal level, especially regarding protective mechanisms against cancer. Cancer can also emerge as a consequence of additional trade‐offs in organisms (e.g., eco‐immunological trade‐offs). Here, we review the wide range of trade‐offs that occur at different scales and their relevance for understanding cancer dynamics. We also discuss how acknowledging these phenomena, in light of human evolutionary history, may suggest new guidelines for preventive and therapeutic strategies.

Can intestinal microbiota be associated with non-intestinal cancers?

While the role of intestinal microbiota is increasingly recognized in the etiology of digestive cancers, its effects on the development of cancer in other parts of the body have been little studied. Through new-generation sequencing, we aimed to identify an association between the structure of intestinal microbiota and the presence of eye disc tumor in Drosophila larvae. First, we observed a parental effect on the diversity and structure of bacterial communities. Second, we identified a bacterial signature (at the family level) of cancer: cancerous larvae host a significantly lower relative abundance of Bacillaceae than individuals that did not develop the tumor. Thus, for the first time, we showed that a non-digestive cancer, i.e., in the brain, could be associated with an altered composition of the gut microbial community. Finally, we discuss the potential implications of the immune system in the gut–brain axis concept to explain the long-distant effect of intestinal microbiota on brain tumors. We also highlight the potential of our results in a therapeutic perspective for brain cancer that could be generalized for other cancers.

Interactions between immune challenges and cancer cells proliferation: timing does matter!

Using first a theoretical framework, we show that repeated short immune challenges could impact the accumulation of cancerous cells through continuous perturbation of immune system efficiency. We discuss for a new indirect role for infectious disease in cancer progression.

Is adaptive therapy natural

Research suggests that progression-free survival can be prolonged by integrating evolutionary principles into clinical cancer treatment protocols. The goal is to prevent or slow the proliferation of resistant malignant cell populations. The logic behind this therapy relies on ecological and evolutionary processes. These same processes would be available to natural selection in decreasing the probability of an organism’s death due to cancer. We propose that organisms’ anticancer adaptions include not only ones for preventing cancer but also ones for directing and retarding the evolution of life-threatening cancer cells. We term this last strategy natural adaptive therapy (NAT). The body’s NAT might include a lower than otherwise possible immune response. A restrained immune response might forego maximum short-term kill rates. Restraint would forestall immune-resistant cancer cells and produce long-term durable control of the cancer population. Here, we define, develop, and explore the possibility of NAT. The discovery of NAT mechanisms could identify new strategies in tumor prevention and treatments. Furthermore, we discuss the potential risks of immunotherapies that force the immune system to ramp up the short-term kill rates of malignant cancer cells in a manner that undermines the body’s NAT and accelerates the evolution of immune resistance.