In vitro competition between two transmissible cancers and potential implications for their host, the Tasmanian devil.

Since the emergence of a transmissible cancer, devil facial tumour disease (DFT1), in the 1980s, wild Tasmanian devil populations have been in decline. In 2016, a second, independently evolved transmissible cancer (DFT2) was discovered raising concerns for survival of the host species. Here, we applied experimental and modelling frameworks to examine competition dynamics between the two transmissible cancers in vitro. Using representative cell lines for DFT1 and DFT2, we have found that in monoculture, DFT2 grows twice as fast as DFT1 but reaches lower maximum cell densities. Using co-cultures, we demonstrate that DFT2 outcompetes DFT1: the number of DFT1 cells decreasing over time, never reaching exponential growth. This phenomenon could not be replicated when cells were grown separated by a semi-permeable membrane, consistent with exertion of mechanical stress on DFT1 cells by DFT2. A logistic model and a Lotka-Volterra competition model were used to interrogate monoculture and co-culture growth curves, respectively, suggesting DFT2 is a better competitor than DFT1, but also showing that competition outcomes might depend on the initial number of cells, at least in the laboratory. We provide theories how the in vitro results could be translated to observations in the wild and propose that these results may indicate that although DFT2 is currently in a smaller geographic area than DFT1, it could have the potential to outcompete DFT1. Furthermore, we provide a framework for improving the parameterization of epidemiological models applied to these cancer lineages, which will inform future disease management.

Transmissible Cancer Evolution: The Under-Estimated Role of Environmental Factors in the "Perfect Storm" Theory.

Although the true prevalence of transmissible cancers is not known, these atypical malignancies are likely rare in the wild. The reasons behind this rarity are only partially understood, but the "Perfect Storm hypothesis" suggests that transmissible cancers are infrequent because a precise confluence of tumor and host traits is required for their emergence. This explanation is plausible as transmissible cancers, like all emerging pathogens, will need specific biotic and abiotic conditions to be able to not only emerge, but to spread to detectable levels. Because those conditions would be rarely met, transmissible cancers would rarely spread, and thus most of the time disappear, even though they would regularly appear. Thus, further research is needed to identify the most important factors that can facilitate or block the emergence of transmissible cancers and influence their evolution. Such investigations are particularly relevant given that human activities are increasingly encroaching into wild areas, altering ecosystems and their processes, which can influence the conditions needed for the emergence and spread of transmissible cell lines.

Ecological and Evolutionary Consequences of Anticancer Adaptations.

Cellular cheating leading to cancers exists in all branches of multicellular life, favoring the evolution of adaptations to avoid or suppress malignant progression, and/or to alleviate its fitness consequences. Ecologists have until recently largely neglected the importance of cancer cells for animal ecology, presumably because they did not consider either the potential ecological or evolutionary consequences of anticancer adaptations. Here, we review the diverse ways in which the evolution of anticancer adaptations has significantly constrained several aspects of the evolutionary ecology of multicellular organisms at the cell, individual, population, species, and ecosystem levels and suggest some avenues for future research.

Transmissible Cancers in an Evolutionary Perspective.

Inter-individual transmission of cancer cells represents an intriguing and unexplored host-pathogen system, with significant ecological and evolutionary ramifications. The pathogen consists of clonal malignant cell lines that spread horizontally as allografts and/or xenografts. Although only nine transmissible cancer lineages in eight host species from both terrestrial and marine environments have been investigated, they exhibit evolutionary dynamics that may provide novel insights into tumor-host interactions particularly in the formation of metastases. Here we present an overview of known transmissible cancers, discuss the necessary and sufficient conditions for cancer transmission, and provide a comprehensive review on the evolutionary dynamics between transmissible cancers and their hosts.