Research update from Dr. Nicola Mason to profile lymphoma and enable targeted therapy.
The clinical response of dogs with lymphoma to chemotherapy is highly variable. Although up to 85% of dogs respond initially, most patients relapse and eventually succumb to their disease. Remission times of dogs with lymphoma are highly variable, some patients relapse within weeks, while others enjoy remission times of several years. This heterogeneity in clinical response is in part explained by the recognition that “lymphoma” is not a single disease entity but consists of different subtypes that can be characterized on a molecular level by mutations in specific genes. As in human medicine, it follows that different lymphoma subtypes, driven by different molecular mechanisms, may respond better to therapies that are specifically selected to inhibit the driver mechanisms within that patient’s tumor. Recent work using sophisticated genetic sequencing tools (next-generation sequencing (NGS)) has begun to shed light on the different molecular subtypes of canine B cell lymphoma and specific therapies aimed at targeting patient specific driver genes and pathways are being developed. To enable targeted therapies to move into the clinic, a personalized diagnostic tool must be developed that can rapidly and cost-effectively determine the mutational profile of a patient’s cancer allowing selection of the most effective drug for that patient. We have designed a next generation sequencing panel that aims to rapidly identify which genes are mutated in a patient’s lymphoma. We are now in the process of validating this panel and optimizing the experimental workflow and bioinformatics associated with it. Once our panel is validated we will use it to determine the specific mutational profiles within canine lymphoma samples, determine whether profiling may predict patient outcome and ultimately whether specific therapies that target the individual patient’s aberrant oncogenic pathway(s) provide superior treatment outcomes when compared with conventional, untargeted chemotherapy.