The evolution of resistance and tolerance as cancer defences

Authors: Thomas, Frederic; Giraudeau, Mathieu; Gouzerh, Flora; Boutry, Justine; Renaud, Francois; Pujol, Pascal; Tasiemski, Aurelie; Bernex, Florence; Maraver, Antonio; Bousquet, Emilie; Dormont, Laurent; Osterkamp, Jens; Roche, Benjamin; Hamede, Rodrigo; Ujvari, Beata.


Brief summary of the paper:

Although there is a plethora of cancer associated-factors that can ultimately culminate in death (cachexia, organ impairment, metastases, opportunistic infections, etc.), the focal element of every terminal malignancy is the failure of our natural defences to control unlimited cell proliferation.

The reasons why our defences apparently lack efficiency is a complex question, potentially indicating that, under Darwinian terms, solutions other than preventing cancer progression are also important contributors. In analogy with host-parasite systems, we propose to call this latter option ‘tolerance’ to cancer.

Here, we argue that the ubiquity of oncogenic processes among metazoans is at least partially attributable to both the limitations of resistance mechanisms and to the evolution of tolerance to cancer.

Deciphering the ecological contexts of alternative responses to the cancer burden is not a semantic question, but rather a focal point in understanding the evolutionary ecology of host-tumour relationships, the evolution of our defences, as well as why and when certain cancers are likely to be detrimental for survival.

Will urbanisation affect the expression level of genes related to cancer of wild great tits?

Authors: Giraudeau, Mathieu; Watson, Hannah; Powell, Daniel; Vincze, Orsolya; Thomas, Frederic; Sepp, Tuul; Ujvari, Beata; et al.


Brief summary of the paper:

Recent studies suggest that oncogenic processes (from precancerous lesions to metastatic cancers) are widespread in wild animal species, but their importance for ecosystem functioning is still underestimated by evolutionary biologists and animal ecologists.

Similar to what has been observed in humans, environmental modifications that often place wild organisms into an evolutionary trap and/or exposes them to a cocktail of mutagenic and carcinogenic pollutants might favor cancer emergence and progression, if animals do not up-regulate their defenses against these pathologies.

Here, we compared, for the first time, the expression of 59 tumor-suppressor genes in blood and liver tissues of urban and rural great tits (Parus major); urban conditions being known to favor cancer progression due to, among other things, exposure to chemical or light pollution.

Contrary to earlier indications, once we aligned the transcriptome to the great tit genome, we found negligible differences in the expression of anti-cancer defenses between urban and rural birds in blood and liver. Our results indicate the higher expression of a single caretaker gene (i.e. BRCA1) in livers of rural compared to urban birds.

We conclude that, while urban birds might be exposed to an environment favoring the development of oncogenic processes, they seem to not upregulate their cancer defenses accordingly and future studies should confirm this result by assessing more markers of cancer defenses.

This may result in a mismatch that might predispose urban birds to higher cancer risk and future studies in urban ecology should take into account this, so far completely ignored, hazard.

Differences in mutational processes and intra-tumour heterogeneity between organs: The local selective filter hypothesis

Authors: Giraudeau, Mathieu; Sepp, Tuul; Ujvari, Beata; et al.


Brief summary of the paper:

Extensive diversity (genetic, cytogenetic, epigenetic and phenotypic) exists within and between tumours, but reasons behind these variations, as well as their consistent hierarchical pattern between organs, are poorly understood at the moment.

We argue that these phenomena are, at least partially, explainable by the evolutionary ecology of organs’ theory, in the same way that environmental adversity shapes mutation rates and level of polymorphism in organisms.

Organs in organisms can be considered as specialized ecosystems that are, for ecological and evolutionary reasons, more or less efficient at suppressing tumours.

When a malignancy does arise in an organ applying strong selection pressure on tumours, its constituent cells are expected to display a large range of possible surviving strategies, from hyper mutator phenotypes relying on bet-hedging to persist (high mutation rates and high diversity), to few poorly variable variants that become invisible to natural defences.

In contrast, when tumour suppression is weaker, selective pressure favouring extreme surviving strategies is relaxed, and tumours are moderately variable as a result. We provide a comprehensive overview of this hypothesis.

Lay summary: Different levels of mutations and intra-tumour heterogeneity have been observed between cancer types and organs. Anti-cancer defences are unequal between our organs. We propose that mostly aggressive neoplasms (i.e. higher mutational and ITH levels), succeed in emerging and developing in organs with strong defences.

Global meta‐analysis of over 50 years of multidisciplinary and international collaborations on transmissible cancers

Authors: Antoine M. Dujon, Gail Schofield, Georgina Bramwell, Nynke Raven, Rodrigo Hamede, Frédéric Thomas & Beata Ujvari

Source: Evolutionary Applications

Brief summary of the paper: Although transmissible cancers have, so far, only been documented in three independent animal groups, they not only impact animals that have high economic, environmental and social significance, but they are also one of the most virulent parasitic life forms.

Currently known transmissible cancers traverse terrestrial and marine environments, and are predicted to be more widely distributed across animal groups; thus, the implementation of effective collaborative scientific networks is important for combating existing and emerging forms.

Here, we quantify how collaborative effort on the three known transmissible cancers has advanced through the formation of collaborative networks among institutions and disciplines. These three cancers occur in bivalves (invertebrates—disseminated neoplasia; DN), Tasmanian devils (vertebrate—marsupial; devil facial tumour disease; DFTD) and dogs (vertebrate—eutherian mammal; canine transmissible venereal tumour; CTVT). Research on CTVT and DN has been conducted since 1876 and 1969, respectively, whereas systematic research on DFTD only started in 2006.

Yet, collaborative effort on all three diseases is global, encompassing six major Scopus subject areas. Collaborations steadily increased between 1963 and 2006 for CTVT and DN, with similar acceleration for all three cancers since 2006. Network analyses demonstrated that scientists are organizing themselves into efficient collaborative networks; however, these networks appear to be far stronger for DFTD and DN, possibly due to the recent detection of new strains adding impetus to research and associated publications (enhancing citation trajectories).

In particular, global and multidisciplinary collaborations formed almost immediately after DFTD research was initiated, leading to similar research effort and relatively greater research outputs compared to the other two diseases.

Therefore, in the event of outbreaks of new lineages of existing transmissible cancers, or the discovery of new transmissible cancers in the future, the rapid formation of international collaborations spanning relevant disciplines is vital for the efficient management of these diseases.

The potential of marginal coastal nursery habitats for the conservation of a culturally important Caribbean marine species

Authors: Thomas C. Stieglitz, Antoine M. Dujon, Joanne R. Peel, Erwan Amice

Source: Diversity and Distributions

Brief summary of the paper:

Aim: Identifying the potential of marginal habitats for species conservation is of key importance when their core high‐quality habitats are under substantial disturbances and threats. However, there is currently a knowledge gap on how useful marine marginal habitats may be for conserving endangered marine species. Here, we investigate the potential of groundwater‐fed coastal areas for the conservation of the queen conch, an economically and culturally important marine gastropod.

Location: The inlet of Xel‐Há, typical of groundwater‐fed coastal areas widely distributed along the Yucatan Peninsula coast in Mexico and partially protected by a network of marine protected areas.

Methods: We tracked 66 queen conchs (Lobatus gigas) using acoustic telemetry over a period of 3.5 years. We investigated for ontogenetic niche shift using a network analysis and by modelling their growth.

Results: The queen conchs exhibited the same ontogenetic niche shift required to complete their life cycle in this marginal habitat as they do in offshore core habitats. A total of 33 individuals departed the inlet and migrated from shallow groundwater‐affected nursery grounds to deeper marine habitats more suitable for breeding aggregation.

Main conclusions: As the broad‐scale movement behaviour of queen conch in this inlet is similar to that observed on the overfished core habitats, our findings suggest that groundwater‐fed coastal areas should be included in conservation planning for an effective management of this species within a network of marine protected areas.

Rare and unique adaptations to cancer in domesticated species: An untapped resource?

Authors: Thomas, Frederic; Giraudeau, Mathieu; Dheilly, Nolwenn M.; Gouzerh, Flora; Boutry, Justine; Beckmann, Christa; Biro, Peter A.; Hamede, Rodrigo; Abadie, Jerome; Labrut, Sophie; Bieuville, Margaux; Misse, Dorothee; Bramwell, Georgina; Schultz, Aaron; Le Loc’h, Guillaume; Vincze, Orsolya; Roche, Benjamin; Renaud, Francois; Russell, Tracey; Ujvari, Beata


Brief summary of the paper: Strong and ongoing artificial selection in domestic animals has resulted in amazing phenotypic responses that benefit humans, but often at a cost to an animal’s health, and problems related to inbreeding depression, including a higher incidence of cancer.

Despite high rates of cancer in domesticated species, little attention has been devoted to exploring the hypothesis that persistent artificial selection may also favour the evolution of compensatory anticancer defences.

Indeed, there is evidence for effective anti‐cancer defences found in several domesticated species associated with different cancer types.

We also suggest that artificial selection can favour the “domestication” of inherited oncogenic mutations in rare instances, retaining those associated to late and/or less aggressive cancers, and that by studying these seemingly rare anticancer adaptations, novel cancer treatments may be found.

Komodo dragons are not ecological analogs of apex mammalian predators

Authors: Tim S. Jessop, Achmad Ariefiandy, David M. Forsyth, Deni Purwandana, Craig R. White, Yunias Jackson Benu, Thomas Madsen, Henry J. Harlow, Mike Letnic

Source: Ecology

Brief summary of the paper: Apex predators can have substantial and complex ecological roles in ecosystems. However, differences in species‐specific traits, population densities, and interspecific interactions are likely to determine the strength of apex predators’ roles.

Here we report complementary studies examining how interactions between predator per capita metabolic rate and population density influenced the biomass, population energy use, and ecological effects of apex predators on their large mammalian prey.

We first investigated how large mammal prey resources and field metabolic rates of terrestrial apex predators, comprising large mammals and the Komodo dragon (Varanus komodoensis), influenced their biomass densities and population energy use requirements. We next evaluated whether Komodo dragons, like apex mammalian predators, exerted top‐down regulation of their large mammal prey. Comparison of results from field studies demonstrates that Komodo dragons attain mean population biomass densities that are 5.75−231.82 times higher than that of apex mammalian predator species and their guilds in Africa, Asia, and North America.

The high biomass of Komodo dragons resulted in 1.96−108.12 times greater population energy use than that of apex mammalian predators. Nevertheless, substantial temporal and spatial variation in Komodo dragon population energy use did not regulate the population growth rates of either of two large mammal prey species, rusa deer (Rusa timorensis) and wild pig (Sus scrofa).

We suggest that multiple processes weaken the capacity of Komodo dragons to regulate large mammal prey populations. For example, a low per capita metabolic rate requiring an infrequent and inactive hunting strategy (including scavenging), would minimize lethal and nonlethal impacts on prey populations. We conclude that Komodo dragons differ in their predatory role from, including not being the ecological analogs of, apex mammalian predators.

Can postfertile life stages evolve as an anticancer mechanism?

Authors: Frédéric Thomas, Mathieu Giraudeau, François Renaud ,Beata Ujvari, Benjamin Roche, Pascal Pujol, Michel Raymond, Jean-François Lemaitre, Alexandra Alvergne

Source: PLOS Biology

Brief summary of the paper: Why a postfertile stage has evolved in females of some species has puzzled evolutionary biologists for over 50 years. We propose that existing adaptive explanations have underestimated in their formulation an important parameter operating both at the specific and the individual levels: the balance between cancer risks and cancer defenses.

During their life, most multicellular organisms naturally accumulate oncogenic processes in their body. In parallel, reproduction, notably the pregnancy process in mammals, exacerbates the progression of existing tumors in females. When, for various ecological or evolutionary reasons, anticancer defenses are too weak, given cancer risk, older females could not pursue their reproduction without triggering fatal metastatic cancers, nor even maintain a normal reproductive physiology if the latter also promotes the growth of existing oncogenic processes, e.g., hormone-dependent malignancies.

At least until stronger anticancer defenses are selected for in these species, females could achieve higher inclusive fitness by ceasing their reproduction and/or going through menopause (assuming that these traits are easier to select than anticancer defenses), thereby limiting the risk of premature death due to metastatic cancers.

Because relatively few species experience such an evolutionary mismatch between anticancer defenses and cancer risks, the evolution of prolonged life after reproduction could also be a rare, potentially transient, anticancer adaptation in the animal kingdom.

Metastasis and the evolution of dispersal

Authors: Tazzio Tissot, François Massol, Beata Ujvari, Catherine Alix-Panabieres, Nicolas Loeuille and Frédéric Thomas


Brief summary of the paper: Despite significant progress in oncology, metastasis remains the leading cause of mortality of cancer patients. Understanding the foundations of this phenomenon could help contain or even prevent it.

As suggested by many ecologists and cancer biologists, metastasis could be considered through the lens of biological dispersal: the movement of cancer cells from their birth site (the primary tumour) to other habitats where they resume proliferation (metastatic sites).

However, whether this model can consistently be applied to the emergence and dynamics of metastasis remains unclear. Here, we provide a broad review of various aspects of the evolution of dispersal in ecosystems.

We investigate whether similar ecological and evolutionary principles can be applied to metastasis, and how these processes may shape the spatio-temporal dynamics of disseminating cancer cells. We further discuss complementary hypotheses and propose experimental approaches to test the relevance of the evolutionary ecology of dispersal in studying metastasis.

Dog attacks on adders; a comment on Worthington‐Hill & Gill (2019)

Authors: T. Madsen, L. Luiselli, P. Janssen


Brief summary of the paper: We have been conducting long‐term studies of adders in Sweden (39 years), The Netherlands (42 years) and in Italy on asp vipers Vipera aspis for 32 years. In spite of the sometimes abundance of dogs, we have never recorded any predation on adders by dogs.

We have, however, recorded many dogs getting bitten. For example, data from the ‘Working group Adder research Netherlands’ show that each year at least 10 dogs are bitten by adders. These bites occur not because of aggressive behaviour by the dogs towards adders, but more due to curiosity.

Similarly to Sweden, in the Netherlands, there are only a few cases recorded where the dog actually died from the bite, which is supported by a study on adder bites on dogs conducted in the UK