Mast Cell Tumors in Dogs: Role of C-Kit Receptor

Mast Cell Tumors in Dogs: Role of C-Kit ReceptorAll mast cells require a certain tyrosine kinase receptor called c-kit, which is a protein on the membrane of the cell, to survive.  Another name for c-kit is stem cell factor (SCF) receptor.   SCF is a growth factor for blood cells and therefore stimulates production of various types of blood cells.  A gene (DNA) exists, which codes for production of the tyrosine kinase protein receptor.  In some but not all mast cell tumors, a mutation in the gene that codes for the c-kit receptor can occur that results in production of a receptor that is always activated or turned on.  This mutation is considered to result in mast cell tumors developing in dogs whose tumors contain a mutated form of the gene.  Mutations of greatest significance tend to occur in the 8 or 11 exon region of this particular gene.  Two new drugs, Palladia and Kinavet (also known as Masivet in Europe), are available that block the activity of the c-kit receptor, and may be effective at treating this type of tumor in dogs.  Response to the drug is more likely in dogs with the mutation, however these drugs can still be effective in dogs without a mutated tyrosine kinase gene.

Palladia and Kinavet as a c-kit receptor inhibitor to treat mast cell tumors in dogs

Palladia and Kinavet are both commercially available oral drugs called small molecule inhibitors of the tyrosine kinase receptor c-kit.  One study showed a decrease in tumor size in 42.8% of dogs with mast cell tumors, however if a mutation of the tyrosine kinase receptor gene was present, response rates were in the 60% range.  Some dogs that do not respond to one drug may be found to respond to the other drug.  Palladia tends to have a greater risk of intestinal side effects and is administered on an every other day or a Monday-Wednesday-Friday dosing schedule.  Kinavet is typically dosed on a daily basis.  If side effects are noted to either drug, they typically resolve very soon after discontinuation of the drug.  More complete information on Palladia can be found in the product information sheet for that drug.  More detailed information on Kinavet can be found at AB Science’s web site.

Testing for mutation of the c-kit receptor gene mutation

It is not always indicated to test a dog’s tumor for a mutation of the tyrosine kinase receptor gene to know if Palladia or Kinavet will be effective for treating a mast cell tumor in a dog.  However, some owners may be inclined to have their dog’s tumor tested to see if a mutation of the gene that codes for the tyrosine kinase receptor exists.  Tissue samples can be sent to certain labs that can run the test on the cells to determine if a mutation exists.  Labs that currently run this type of test include Colorado State University, Michigan State University, University of Missouri and North Carolina State University.  Only Colorado State University tests for mutations at exon sites 8 and 11, while the other universities test only for mutation at exon site 11.

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Dr Stephen Atwater

Stephen W. Atwater, DVM, MS, Diplomate ACVIM (oncology) is a board-certified veterinary oncology specialist. His professional interests include utilizing emerging therapies for difficult to treat cancers.

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