Presenter – Douglas H. Thamm, Assistant Professor of Oncology, Colorado State University How much do I really know about chemotherapy agents? I know their names and what conditions to use them for but when asked the question: 'how exactly do they work?' I can only deliver a very simplistic explanation. Last week's veterinary webinar run by 'The Webinar vet' helped to re-enforce my understanding of one particular class of drug relatively new to the veterinary world, the receptor tyrosine kinase inhibitors. Associate Professor Douglas H. Thamm led this veterinary webinar and discussed the potential for these drugs both now and in the future. He started by explaining that in order to grasp the benefits of the receptor tyrosine kinase inhibitors, the role of the receptor tyrosine kinase (RTK) needed to be understood. RTK is a protein that spans the surface of cells and listens to the extracellular environment, influencing cellular behaviour when necessary. These receptors can become deregulated by changes such as mutations which cause them to become easily activated. If signalled, they enhance cellular proliferation, cellular survival, migration and invasion. They also enhance angiogenesis and with all these factors combined will eventually lead to metastasis and 'cancer'. The RTK inhibitors should help to down regulate these mutated genes, the most notable of which is C-KIT, which is present on both normal and malignant canine mast cells. Around 20-40% of canine mast cell tumours have a mutation in their C-KIT gene leading to constant activation. This explains why the RTK inhibitors we are most familiar with, Toceranib ('Palladia') and Masitinib ('Masivet') are used to treat this common tumour. Prof. Thamm went into a lot of detail outlining the benefits of both these products in the treatment of canine mast cell tumours and the role of the C-KIT gene. However from these publications came a lot more questions about the use of these drugs in treating cancer. For example when treating canine mast cell tumours, should the RTK inhibitors be used in combination with other treatments, such as other chemotherapy agents and radiation therapy?

Currently Prof. Thamm's standard therapy for nonresectable localised MCTs is to use radiation therapy, toceranib and prednisolone based on this combination offering disease control for 10.5 months. Prof. Thamm is also hoping to publish research in the near future looking into the use of pulsed toceranib with lomustine in order to reduce cost and minimise side effects.

Questions also have to be asked about the use of these drugs post operatively in cases where there has been incomplete excision or where tumours are at high risk of metastasising. Vets are already likely to be using RTK inhibitors post operatively but currently there is no evidence to demonstrate how effective these medications are. There may also be uses for RTK inhibitors in tumours other than canine mast cells, as is the case in the human field. Tumours including osteosarcomas, squamous cell carcinomas and anal sac adenocarcinomas are all potential candidates.

This was an excellent veterinary webinar, with Prof. Thamm explaining difficult concepts in an interesting and understandable way. The RTK-inhibitors are an exciting advancement in our fight against cancer and I suspect we will be hearing a lot more about them in the future.

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