TYROSINE KINASE AND THEIR INHIBITORS:
Receptor tyrosine kinases (RTKs) are molecules on the surface of cells that bind growth factors which circulate in the blood. Under normal conditions, when the growth factor binds to the receptor, this turns ‘on’ signals to the cell which regulates functions such as cell growth, cell survival, the ability to move and spread, and angiogenesis (development of new blood vessels). In some tumors, this normal process is disrupted due to genetic changes (called mutations) in the receptors or in the growth factors. These genetic changes may cause the receptor to be continuously switched into the ‘on’ position even when the growth factor is not attached to the receptor. If the receptor is continuously ‘on’ this leads to continuous cell growth, leading to tumor growth and spread.
Examples of surface RTKs include Kit, epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), and platelet-derived growth factor receptor (PDGFR). Alterations in these RTKs can lead to uncontrolled cell growth and survival and is one of the many underlying causes of some cancers. Examples in veterinary medicine include abnormalities in the Kit receptor in mast cell tumors in dogs and cats as well as gastrointestinal stromal tumors in dogs. Abnormal function of the VEGF and PDGF receptors are likely to present in a variety of canine and feline cancers including feline injection site sarcomas, osteosarcoma, anal gland carcinoma, squamous cell carcinoma (canine and feline), hemangiosarcoma, thyroid carcinoma, and nasal carcinoma. Currently, toceranib phosphate (Palladia; Pfizer Animal Health) is fully licensed and Masitinib (Kinavet, AB-Sciences) is conditionally licensed by the FDA, for treatment in canine mast cell tumors.
These two oral medications are available for use in dogs and several new similar medications are under investigation. Several studies are currently underway evaluating the usefulness of these medications in treating a variety of tumor types including squamous cell carcinoma, osteosarcoma, nasal carcinoma, thyroid carcinoma, vaccine-associated sarcoma, hemangiosarcoma, and anal gland carcinoma. Due to their novel mechanism of action in attacking cancer cells, they can be used alongside our current standard therapies consisting of surgery, radiation therapy, and chemotherapy.
The US Food and Drug Administration recently announced that it granted conditional approval for the first new animal drug to treat canine lymphoma. The FDA said the active ingredient in Tanovea-CA1 is rabacfosadine, a substance that kills rapidly growing cancer cells.
Tanovea-CA1 must be prescribed by a licensed veterinarian because professional expertise is needed to correctly diagnose lymphoma in dogs, determine the best treatment, and manage potential side effects. Tanovea-CA1, which comes in a concentrated form, is diluted and given in a vein over 30 minutes. The infusion should be given by or under the supervision of a veterinarian experienced in chemotherapy.
The “CA1” in Tanovea-CA1 means the drug is conditionally approved. Only animal drugs intended for minor species, such as ferrets or fish, or for minor uses in a major species, such as to treat certain types of cancer in dogs, are eligible for conditional approval. Tanovea-CA1’s conditional approval means that when used according to the label, the drug is safe and has a “reasonable expectation of effectiveness” for treating lymphoma in dogs.
At Hope Veterinary Specialists, our oncology service is excited to add this agent to our current list of drugs to treat lymphoma. We have been using this drug as part of clinical trials for the past several years.