Transmissible Tumors: Breaking the Cancer Paradigm

Abstract

Transmissible tumors are those that have transcended the bounds of their incipient hosts by evolving the ability to infect another individual through direct transfer of cancer cells; thus becoming parasitic cancer clones. Coitus, biting, and scratching are transfer mechanisms for the two primary species studied, the domestic dog (Canis lupus familiaris) and the Tasmanian devil (Sarcophilus harrisii). Canine transmissible venereal tumors (CTVT) are likely thousands of years old, and have successfully travelled from host to host around the world, while the Tasmanian devil facial tumor disease (DFTD) is much younger and geographically localized. The dog tumor is not necessarily lethal, while the devil tumor has driven the population to near extinction. Transmissible tumors are uniform in that they have complex immunologic profiles, which allow them to escape immune detection by their hosts, sometimes for long periods of time. In this review we explore how transmissible tumors in CTVT, DFTD, and as well as the soft-shelled clam and Syrian hamster can advance studies tumor biology.

Oncogenesis as a Selective Force: Adaptive Evolution in the Face of a Transmissible Cancer

“…Persistent challenges by pathogens (including transmissible cancers), will eventually select for increased frequency of resistance‐conferring alleles, or even for the emergence of resistant genotypes that provide transgenerational protection to the pathogens. For example, dogs carry the signature of selective responses to another naturally occurring transmissible cancer, canine venereal tumour disease (CTVT) . This transmissible cancer is considered to be the oldest known somatic cell line and has been proposed to have appeared between 6000 and 11 000 years ago (exact date is still debated) in a post‐domestication canid .…”

“…For example, dogs carry the signature of selective responses to another naturally occurring transmissible cancer, canine venereal tumour disease (CTVT) . This transmissible cancer is considered to be the oldest known somatic cell line and has been proposed to have appeared between 6000 and 11 000 years ago (exact date is still debated) in a post‐domestication canid . Although CTVT impairs the reproduction of dogs at the time of infection, the disease is rarely fatal, strongly suggesting that the dog's immune system has evolved to recognise and suppress tumour growth and eventually achieving complete tumour regression…”

“…[91,92] This transmissible cancer is considered to be the oldest known somatic cell line and has been proposed to have appeared between 6000 and 11 000 years ago (exact date is still debated) in a post-domestication canid. [91][92][93][94] Although CTVT impairs the reproduction of dogs at the time of infection, the disease is rarely fatal, strongly suggesting that the dog's immune system has evolved to recognise and suppress tumour growth and eventually achieving complete tumour regression. [95] Since transmissible cancer cell lines evolve on the evolutionary landscape of the host genomes, a sufficiently high prevalence of a transmissible cancer can result in a tug-of-war akin to hostparasite interactions between the selfish malignant cell lines and host genomes (sensu 'Red-Queen' dynamics).…”

Precision wildlife medicine: applications of the human‐centred precision medicine revolution to species conservation

“…Devil facial tumour disease results in an extremely high rate of adult fatalities, with some wild populations already having been reduced by 95% (Deakin & Belov, 2012). Directly transmissible cancers, in which the pathogen is a clonal infectious cell line originating in a single individual and then spread through injurious contact, were considered to be extremely rare in nature (Welsh, 2011;Ostrander et al, 2016). The recent discovery of a second, histologically different form of DFTD, known as DFT2, therefore suggests that either Tasmanian devils are particularly prone to this kind of disease or transmissible cancers are more prevalent in the wild than had been previously thought (Pye et al, 2016).…”

Possible mechanisms of transmissible cancers in Tasmanian devils

“…Once the devil that is 'infected' with DFTD dies from the cancer. Transmissible tumors have a very complex property, which allow them to escape immune detection both in Tasmanian devil and/or domestic dog (Canis lupus familiaris) [6,7]. DFTD caused the majority of diseased populations died and if this decline continues, species could face extinction because DFTD acts as an infectious disease [3].…”