Nav: Home

Cross-species cancer comparison uncovers new drug targets, study reveals

February 12, 2019

New drug targets for a rare form of melanoma may result from the discovery of similar genetic mutations found in humans, dogs and horses under a first-ever tri-species DNA sequencing study involving a University of Guelph researcher.

Melanoma is a cancer that most commonly occurs in the skin in people, but a subtype called mucosal melanoma arises in non-skin locations such as sinuses, nasal passages and mouth. Oral melanoma in dogs is much more common than in humans and also has a poor prognosis, while melanoma in horses is generally less aggressive.

Currently there are no known risk factors for this cancer in humans, which is often diagnosed late. In all species, the main treatment is surgical removal of the tumour.

Published in Nature Communications, the study was designed to pinpoint key genes that are mutated in mucosal melanoma.

The study was the first to compare cancer genomes across human, canine and equine tumours, the first to sequence horse tumours and the first sequencing study of this scale on dog melanoma.

Comparing cancers across species may help in pinpointing the most relevant drug targets, said pathobiology researcher Geoffrey Wood, assistant co-director of U of G's Institute for Comparative Cancer Investigation (ICCI).

He conducted the study with David Adams, Kim Wong and their collaborators at the Wellcome Trust Sanger Institute in Cambridge, U.K.

"This study is a great example of using a 'one health' approach to leverage similarities and differences across species and find mutations in cancer driver genes -- mutations in genes that are central to the behaviour of the cancer cell and cause it to become malignant," said Wood.

"It can be hard to find those drivers as cancer genomes are full of random mutations that do not impact the cell's behaviour very much. But if you find commonly mutated genes across multiple species in the same cancer type, they are likely driver genes and could be targeted for the development of new therapies."

The research team sequenced the genomes of mucosal melanoma tumours from 46 humans, 65 dogs and 28 horses. Numerous canine and equine samples were contributed to the study by Wood and the Companion Animal Tumour Sample Bank, part of the ICCI.

The team discovered a handful of genes that were commonly mutated in all species.

Interest has grown in the use of immunotherapy, or vaccine therapy, to treat melanoma in humans and dogs, said Wood. But the study found far fewer mutations in mucosal melanoma than in skin melanoma.

With fewer mutations, this cancer may be more difficult for the immune system to detect. That might explain why current immunotherapy often fails in oral melanoma in dogs and mucosal melanoma in humans, he added.

"Understanding the genetic changes underpinning mucosal melanoma suggests why people with this particular type of cancer may not benefit from immunotherapies," said Wong, lead author of the study.

Using this cross-species approach has some added advantages, explained Wood.

"Spontaneous tumours in dogs are gaining recognition as 'models' of human cancers for the development of therapies that can benefit both species," he added. "This study shows the importance of understanding the genetic similarities and differences of cancers across species so that the most biologically relevant drug targets are prioritized."
-end-


University of Guelph

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related Cancer Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Changing The World
What does it take to change the world for the better? This hour, TED speakers explore ideas on activism—what motivates it, why it matters, and how each of us can make a difference. Guests include civil rights activist Ruby Sales, labor leader and civil rights activist Dolores Huerta, author Jeremy Heimans, "craftivist" Sarah Corbett, and designer and futurist Angela Oguntala.
Now Playing: Science for the People

#521 The Curious Life of Krill
Krill may be one of the most abundant forms of life on our planet... but it turns out we don't know that much about them. For a create that underpins a massive ocean ecosystem and lives in our oceans in massive numbers, they're surprisingly difficult to study. We sit down and shine some light on these underappreciated crustaceans with Stephen Nicol, Adjunct Professor at the University of Tasmania, Scientific Advisor to the Association of Responsible Krill Harvesting Companies, and author of the book "The Curious Life of Krill: A Conservation Story from the Bottom of the World".