Could the results of a unique new study that looks at mast cell tumors — which cause a common skin cancer in dogs — lead to drugs that could someday cure the disease?
A recent research study has contributed “an important piece” in the “mast cell tumor jigsaw,” according to Mike Starkey, head of molecular oncology at the Animal Health Trust Center for Small Animal Studies. The research, says Starkey, provides an insight into the types of drug that may prevent tumors from spreading.
“It is the first study that has been really able to look at the genetic changes that promote the metastasis of cutaneous mast cell tumors, one of the most common tumors in dogs,” Starkey notes.
The research was conducted in conjunction with the University of Liverpool Small Animal Teaching Hospital clinical oncology units, and was published in the journal PLOS One.
Mast Cells — The “Jekyll and Hyde” of Tumor Growth
Mast cells have been called the Jekyll and Hyde of tumor growth because they can be both beneficial and detrimental in a tumor. “Mast cells are involved in the body’s immune responses to bacteria, ticks and intestinal parasitic worms, but they also cause allergic reactions that contribute to diseases such as asthma, rhinitis and atopic dermatitis,” explains Starkey.
“We compared the levels of the initial products — called ‘messenger RNAs’ — of about 20,000 genes in 20 primary cutaneous mast cell tumors that metastasized and 20 primary cutaneous mast cell tumors that did not metastasize, and found differences between the levels of over 200 gene products,” says Starkey. “The majority of the gene products were present at a lower level in the mast cell tumors that metastasized. Based on what is known about the genes concerned, it appears that reductions in the levels of the gene products assists cancerous mast cells to detach from surrounding cells in a primary tumor and gives them the ability to move.”
The mast cell tumors included in the research study were from 12 breeds, including Labrador and golden retrievers, and boxers, and 6 cross breeds.
Promising Research into the Mast Cell Tumor Metastasis Mechanism
As for why the research is so promising, Starkey says that “by identifying genes for which a change in gene product level is associated with cutaneous mast cell tumor metastasis, we have identified targets for potential new drugs designed to prevent mast cell tumor metastasis.
“A number of the genes identified are known to be involved in the metastasis of human tumors and drugs targeting some of these genes are already in clinical trials, or being investigated in preclinical studies. Such drugs could ultimately be trialed on dogs with mast cell tumors that are predicted to metastasize,” he notes.
What’s Next in Mast Cell Tumor Research
What’s next for the researchers? “In our research study we showed that by considering the levels of 19 gene products in a primary mast cell tumor it was possible to accurately determine if the mast cell tumor was a tumor that did, or did not, metastasize,” says Starkey. “In the next stage of our research we want to demonstrate that measuring the levels of these 19 gene products, or a smaller subset of them, can consistently accurately determine if a mast cell tumor is one that metastasized, or did not metastasize. To do this we hope to secure the help of vets to assemble a new, larger group of primary cutaneous mast cell tumors that are known definitively to have, or have not, metastasized. We hope that this research will lead to the development of test that will predict whether a cutaneous mast cell tumor will metastasize with an extremely high degree of accuracy, and that could be run on fine needle aspirates of mast cell tumors (collected without anesthesia and surgery).
“Our future research will also attempt to establish the causes of each of the changes in the levels of the gene products in mast cell tumors that promote mast cell tumor metastasis. Several possible causes could themselves be targets for the development of new anti-metastasis drugs.”
Read our overview of Canine Multicentric Lymphoma.