Evolution of natural resistance to cancer: Peto’s paradox revisited – EVOCAN

This is a resubmission of a project submitted last year. The main criticisms were 1) too many unrelated topics, 2) certain tasks involve the acquisition of data already published in the literature and 3) no preliminary data. Our project has been carefully revised in several ways: 1) the project is now exclusively centered on Peto’s paradox, 2) all the research we propose is new and self-contained and 3) certain questions addressed by EvoCan have been the topic of an opinion paper recently published in BMC Cancer by three task leaders of this project, supporting the idea that this research project is topical and that a synergy already exists between project participants.
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Cancer is a disease associated with clonal evolution and cell competition within the body and appeared with the transition to multicellularity more than half a billion years ago. Specifically, somatic cellular selection and evolution are fundamental processes leading to malignancy, with its many manifestations: neoangiogenesis, evasion of the immune system, metastasis and resistance to therapies. Although these ideas originated in the mid-seventies, historically little attention has been focused on applications of evolutionary biology to understand the origin of cancers, to control neoplastic progression and to prevent therapeutic failures. This is now beginning to change and new applications of evolutionary biology are transforming our understanding of cancer (Special issue Evolution and Cancer, Evolutionary Applications, 2013). However, there is still only a limited number of scientists, mostly in North America and very recently in France, that are actively involved in pursuing the interdisciplinary research anchored in the evolutionary view of cancer emergence and progression. The EvoCan project aims at improving our understanding of the evolution of natural resistance/susceptibility to cancers. Assessing natural selection in human populations is challenging, but exploring the rules that govern incidences of cancers in wildlife species is expected to be especially relevant in understanding how natural selection may have moulded human cancer incidence. Specifically, we need to understand the mechanisms underlying the so-called “Peto’s paradox”—the absence of a correlation across species between cancer and body size × longevity. Understanding how large, long-lived species overcome the burden of cancer can indeed provide critical insights into the identification of processes that prevent carcinogenesis. The objectives of EvoCan are to understand the evolutionary causes of Peto’s paradox by exploring the relevance of several novel hypotheses, some of them having been recently proposed in an opinion paper by us in BMC cancer. The project builds on the research program of the recently created CEECR Institute (Center for Ecological and Evolutionary Cancer Research) in Montpellier, as well as the French interdisciplinary research network on Cancer “DarEvCan”. Concretely, EvoCan is structured in four main topics underlying Peto’s paradox, namely (i) Establishing a database on cancer incidence and diversity in wildlife species using zoological park data, (ii) Understanding the influence of species ecology on the evolution of natural resistance to cancers (iii) Is there a Peto’s paradox between organs at the intraspecific level? (iv) What are the influences of cell turnover and metabolic rates on cancer dynamics? Finally we will organize an international workshop on the evolution of natural resistance to cancer and Peto’s Paradox. The evolutionary perspective of cancer has only gained significant international recognition over the past decade. We believe that this project is a unique opportunity to start and promote research in France that adopts a very different, but complementary, perspective on evolution and cancer than current mainstream approaches.