Human drugs could treat transmissible cancers in Tasmanian devils

  • April 9, 2018
Human drugs could treat transmissible cancers in Tasmanian devils

New research paper on which Maximilian Stammnitz is first author looks at transmissable cancers in Tasmanian devils.

When fighting, Tasmanian devils often bite their opponent’s face, which may predispose these animals to the emergence of this particular type of cancer via tissue injury,” adds Stammnitz. “As biting occurs on the face, this would simultaneously provide a route of cell transmission.

Maximilian Stammnitz

Transmissible cancers are incredibly rare in nature, yet have arisen in Tasmanian devils on at least two separate occasions. A new research paper, on which Gates Cambridge Scholar Maximilian Stammnitz is first author, identifies key anti-cancer drugs which could be trialled as a treatment for these diseases, which are threatening Tasmanian devils with extinction.

The research also found that the two Tasmanian devil transmissible cancers are very similar to each other, and likely both arose due to susceptibilities inherent to the devils themselves.

Tasmanian devils are marsupial carnivores endemic to the Australian island of Tasmania. The species is considered endangered due to devil facial tumour 1 (DFT1), a cancer that is passed between animals through the transfer of living cancer cells when the animals bite each other. DFT1 causes grotesque and disfiguring facial tumours, which usually kill affected individuals.

The DFT1 cancer first arose in a single individual devil several decades ago, but rather than dying together with this devil, the cancer survived by ‘metastasising’ into different devils. Therefore, the DNA of the devils’ tumour cells is not their own DNA, but rather belongs to the individual devil that first gave rise to DFT1 all those years ago. Remarkably, DFT1 cells can escape the devils’ immune systems despite being in essence a foreign body.

The DFT1 cancer was first observed in north-east Tasmania in 1996, but has subsequently spread widely throughout the island, causing significant declines in devil populations.

In 2014, routine diagnostic screening revealed a second transmissible cancer in Tasmanian devils, devil facial tumour 2 (DFT2), which causes facial tumours indistinguishable to the naked eye from those caused by DFT1, and which is probably also spread by biting. However, analysis showed that the two types of cancer differ at a biological level, and whereas DFT1 first arose from the cells of a female devil, DFT2 appears to have first arisen from a male animal. For now, DFT2 appears to be confined to a peninsula in Tasmania’s south-east.

“The discovery of a second transmissible cancer in Tasmanian devils was a huge surprise,” says Dr Elizabeth Murchison from the Department of Veterinary Medicine at the University of Cambridge. “Other than these two cancers, we know of only one other naturally occurring transmissible cancer in mammals – the canine transmissible venereal tumour in dogs, which first emerged several thousand years ago.”

In fact, outside of mammals, only five transmissible cancers have been observed, all of which cause leukaemia-like diseases in clams and other shellfish.

“The scarcity of transmissible cancers suggests that such diseases emerge rarely,” she adds. “Before 1996, no one had observed them in Tasmanian devils, so finding two transmissible cancers in Tasmanian devils in just 18 years was very surprising.”

In order to see whether the devil transmissible cancers are caused by external factors or whether the animals were just particularly susceptible to developing these cancers, a research team led by Dr Murchison analysed the genetic profiles of DFT1 and DFT2 tumours taken from a number of Tasmanian devils. The results are published today in the journal Cancer Cell.

The team found striking similarities in tissues-of-origin, genetics, how the cancer cells mutate, and possible drug targets. This implies that the two tumours belong to the same cancer type and arose via similar mechanisms.

The team studied the genetic and physical features of the tumours, and compared the two lineages with each other and with human cancers. In doing so, they identified an important role in the tumours for particular types of molecules known as receptor tyrosine kinases (RTKs) in sustaining growth and survival of DFT cancers.

Importantly, drugs targeting RTKs have already been developed for human cancer, and the researchers showed that these drugs efficiently stopped the growth of devil cancer cells growing in the lab. This leads to hope that it may be possible to use these drugs to help Tasmanian devils.

Biting on the face

First author of the study, Gates Cambridge Scholar Maximilian Stammnitz [2016], adds: “Altogether, our findings suggest that transmissible cancers may arise naturally in Tasmanian devils. We found no DNA-level evidence of these cancers being caused by external factors or infectious agents such as viruses. It seems plausible that similar transmissible cancers may have occurred in the past, but escaped detection, perhaps because they remained in localised populations, or because they existed prior to the arrival of Europeans in Tasmania in the 19th century.”

Why Tasmanian devils should be particularly susceptible to the emergence of DFTs is not clear. However, devils bite each other frequently around the facial area, often causing significant tissue injury. Given the important role for RTK molecules in wound healing, the researchers speculate that DFT cancers may arise from errors in the maintenance of proliferative cells involved in tissue repair after injury.

“When fighting, Tasmanian devils often bite their opponent’s face, which may predispose these animals to the emergence of this particular type of cancer via tissue injury,” adds Stammnitz. “As biting occurs on the face, this would simultaneously provide a route of cell transmission.”

The researchers say it is also possible that human activities may have indirectly increased the risk of the emergence or spread of transmissible devil facial tumours (DFTs) in recent years. For instance, it is possible that some modern land use practices may have provided favourable conditions for devils, leading to an increase in local population densities of devils, and to greater competition, interactions and fights between animals, which may in turn have raised probabilities of DFTs arising or spreading. Alternatively, early persecution of devils by European colonists may have additionally contributed to this species' documented low genetic diversity, a possible risk factor for disease spread and the ability of DFTs to escape the immune system.

The researchers also identified deletions in DFT1 and in DFT2 in genes involved in recognition of cancer cells by the immune system. This may help explain how these cancers escape the immune system.

“The story of Tasmanian devils in recent years has been a very concerning one,” says Dr Murchison. “This study gives us optimism that anti-cancer drugs that are already in use in humans may offer a chance to assist with conservation efforts for this iconic animal.”

The research was funded by Wellcome, the National Science Foundation, Save the Tasmanian Devil Program, Leverhulme Trust, Cancer Research UK and Gates Cambridge Trust.

Maximilian Stammnitz

Maximilian Stammnitz

  • Alumni
  • Germany
  • 2016 PhD Veterinary Medicine
  • Pembroke College

As a PhD student in the Transmissible Cancer Group of Dr. Elizabeth Murchison (2015 - 2020), I have worked on Transmissible Tasmanian Devil Facial Tumour Disease (DFTD) genetics through computational analyses of large-scale DNA and RNA sequencing data. I am now an EMBO fellow at the Centre for Genomic Regulation, Barcelona.

Latest News

21st century curator

Even while he was doing his PhD in art history, Julien Domercq was not only getting involved in the British art scene, he was curating one of the biggest art exhibitions of the day. Julien [2013] had taken up a two-year entry-level contract at the National Gallery a couple of years into his PhD on […]

Understanding migrant stories

Two Gates Cambridge Scholars are collaborating on a new research, story-telling and advocacy enterprise which aims to record journeys of migration, amplify the voices of migrants and build empathy for the growing number of people who are displaced or have to leave their country. Noor Shahzad, founder at Migration Collective, became interested in the stories […]

Gates Cambridge Class of 2024 announced

The Gates Cambridge Class of 2024 made up of 75 outstanding new scholars has been officially announced. The Gates Cambridge scholarship programme is the University of Cambridge’s flagship international postgraduate scholarship programme. It was established through a US$210 million donation to the University of Cambridge from the Bill and Melinda Gates Foundation in 2000. Since […]

Addressing the mental health emergency

Mental health has been rising up the global health priority list over the last few years, but Covid accelerated it. Yet the resources available to those in crisis situations are few. Gates Cambridge Scholar Usama Mirza is addressing one particular gap in his home country of Pakistan, having recently launched Asia’s first mental health ambulance […]