Transmissible cancers in an evolutionary context

Abstract

Cancer is an evolutionary and ecological process in which complex interactions between tumour cells and their environment share many similarities with organismal evolution. Tumour cells with highest adaptive potential have a selective advantage over less fit cells. Naturally occurring transmissible cancers provide an ideal model system for investigating the evolutionary arms race between cancer cells and their surrounding micro-environment and macro-environment. However, the evolutionary landscapes in which contagious cancers reside have not been subjected to comprehensive investigation. Here, we provide a multifocal analysis of transmissible tumour progression and discuss the selection forces that shape it. We demonstrate that transmissible cancers adapt to both their micro-environment and macroenvironment, and evolutionary theories applied to organisms are also relevant to these unique diseases. The three naturally occurring transmissible cancers, canine transmissible venereal tumour (CTVT) and Tasmanian devil facial tumour disease (DFTD) and the recently discovered clam leukaemia, exhibit different evolutionary phases: (i) CTVT, the oldest naturally occurring cell line is remarkably stable; (ii) DFTD exhibits the signs of stepwise cancer evolution; and (iii) clam leukaemia shows genetic instability. While all three contagious cancers carry the signature of ongoing and fairly recent adaptations to selective forces, CTVT appears to have reached an evolutionary stalemate with its host, while DFTD and the clam leukaemia appear to be still at a more dynamic phase of their evolution. Parallel investigation of contagious cancer genomes and transcriptomes and of their microenvironment and macro-environment could shed light on the selective forces shaping tumour development at different time points: during the progressive phase and at the endpoint. A greater understanding of transmissible cancers from an evolutionary ecology perspective will provide novel avenues for the prevention and treatment of both contagious and non-communicable cancers.

Infection of the fittest: devil facial tumour disease has greatest effect on individuals with highest reproductive output

“…Our estimates of the time until death following infection are longer than the 6 months previously reported Ujvari et al 2016). These previous estimates were for time until death after first detection of tumours.…”

“…; Ujvari et al . ). These previous estimates were for time until death after first detection of tumours.…”

Short‐ and long‐term evolution in our arms race with cancer: Why the war on cancer is winnable

“…In fact, cancer cells have no long‐term evolutionary potential at all. Rather, a defining feature of oncogenic or intrasomatic selection is that it is constrained to act as a short‐term, discontinuous, or episodic process, with each episode confined to events occurring within a single host, and ending abruptly when that host dies (from whatever cause) or the cancer is cured, eradicating all cancer cells (Aktipis & Nesse, ; Arnal et al., ; Crespi & Summers, ; Ewald & Swain Ewald, ; Haig, Merlo, Pepper, Reid, & Maley, ; Ujvari, Papenfuss, & Belov, b). Resistance adaptations, like any other adaptations that might evolve in cancers, thus cannot persist beyond the death of each host—there is simply no way for cancer cell lines (or, at least, noninfectious cancer cell lines—see below) to pass adaptations to a new host.…”

“…Finally, we have the case of contagious cancers, in which cancer cells themselves are capable of moving between different host individuals. Infectious cancers have been found in dogs, Tasmanian devils, and a diverse group of marine gastropods (Metzger & Goff, ; Metzger et al., ; Ujvari, Gatenby, & Thomas, ; Ujvari, Papenfuss et al., ), but, happily, not in human populations. An infectious human cancer would be a nightmare scenario for resistance evolution, as the powerful short‐term evolutionary potential of cancer cells would be extended to a longer‐term, continuous process.…”

“…Although the genomic instability of most human cancers might not be sustainable over longer periods of time, due to catastrophic mutation accumulation (Andor, Maley, & Ji, ; Arnal et al., ), the strong mortality imposed on host populations by some newly emerged contagious cancers (Epstein et al., ; Metzger & Goff, ) shows how fortunate we are that we lack any such cell lines. Our highly polymorphic major histocompatibility complex (MHC) loci are likely our primary defense against the future emergence of such cancers (Ujvari, Gatenby et al., ; Ujvari, Papenfuss et al., ).…”