The clinical response of dogs with lymphoma to multi-agent chemotherapy is highly variable. Although up to 85% of dogs respond initially, some relapse within weeks, while others enjoy remission times of two 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.
Supported by the AKC-CHF, we have developed a NGS diagnostic test that can be employed on standard biopsy samples to identify molecular drivers of a patient’s lymphoma (personalized diagnostics). This will enable targeted therapies to be selected based on their ability to inhibit the molecular pathway that is driving that specific patient’s tumor.
We are in the process of using our NGS panel to evaluate 100 canine lymphoma samples and determine their tumor mutational burden and molecular drivers. In addition, we aim to determine whether specific mutational profiles within canine lymphoma identified by our NGS panel, are predictive of outcome. This is an important first step toward bringing personalized diagnostics that aim to improve the outcome of patients with B cell lymphoma, into the veterinary clinic.
Mid-Year-3 Research Update Dr. Mason for precision therapy for lymphoma.
