Project Categories: Cancer

The most common type of cancer in dogs is lymphoma, with ~80,000 cases diagnosed annually in the United States. Breeds vary in their risk of lymphoma, but it is unclear why there is variation despite considerable effort to identify the genetics of cancer risk and progression in dogs. Cancer typically arises from the accumulation of non-inherited (i.e. somatic) mutations. However, variation among breeds in cancer risk could be due to breed-specific variation in the types of mutations, the rate of accumulation of mutations, or the downstream effects of mutations in healthy dogs.

This study will use novel sequencing technology to test the hypothesis that breed-specific lymphoma risk is due to variation in the frequency and type of rare precancerous mutations. Normally, measuring these low-frequency mutations has been beyond the range of standard sequencing technology, which is limited to detecting mutations present in >1% of cells. The new technology applied here represents a >10,000-fold improvement in accuracy, enabling the investigators to accurately detect a precancerous mutation present at a single site at a frequency of just one out of every 10 million DNA base pairs. By determining if mutation frequency in blood of healthy high-risk and low-risk dogs can predict lymphoma risk, this work could lead to the development of novel tests for the early diagnosis and prognosis of canine lymphoma.

This work has the potential to shed light on the mechanisms that underlie breed-specific variation in lymphoma risk, and in the long term, could lead to the development of novel tests for the early diagnosis and prognosis of canine lymphoma.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 2772

RESEARCHERS

Daniel Promislow, PhD; University of Washington
Amount: $10,000

Skin cancer is common in older dogs and often requires surgery to treat. For these tumors, the best chance of cure is offered if the surgeon can fully remove both visible and microscopic traces of the tumor. Currently surgeons must rely on pathologist’s assessment of tissues after surgery and the success of the procedure will not be known until several days later. This result is important as residual cancer may need further surgery or other treatments like radiation therapy. Additional treatments such as these can result in further risk and discomfort for dogs as well as be an emotional and financial cost for owners. Optical coherence tomography is an emerging diagnostic imaging tool that uses light waves to generate real-time, high-resolution images of tissue at a microscopic level. These images can be used to evaluate for residual disease at the time of surgery giving immediate feedback to the surgeon.

This study will focus on validating this technology for the imaging of surgical margins of canine skin and subcutaneous tumors. If successful, this technology could be used to assess for residual cancer intra-operatively to benefit patients by guiding accurate treatment recommendations.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 2758

RESEARCHERS

Laura Selmic, BVetMed, MPH; Ohio State University Research Foundation
Amount: $5,000

Bladder cancer is an aggressive cancer that affects ~ 20,000 dogs per year, and often leads to euthanasia. Certain breeds have a higher incidence of bladder cancer but genetic studies even in the highest risk breeds have been inconclusive and still indicate influence from environmental exposures. The investigators propose that specific household environmental chemical exposures contribute to the risk of bladder cancer in dogs.

In this study, they will measure urinary concentrations of five different chemicals that are known or suspected to be bladder carcinogens, in dogs with bladder cancer compared to unaffected dogs. The investigators will determine whether the presence of certain chemicals is associated with household exposures, based on owner questionnaires and household proximity to industrial sites. Finally, they will determine whether urinary chemical concentrations are linked to early DNA damage in the urinary cells of healthy dogs that do not have bladder cancer. The overall goal of this study is to provide veterinarians and dog owners with evidence-based bladder cancer prevention strategies.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 2780

RESEARCHERS

Lauren Trepanier, DVM, PhD; University of Wisconsin, Madison
Amount: $15,000

Soft tissue sarcomas account for 10-15% of all skin and subcutaneous cancers in dogs. Traditionally, biopsy and subsequent histology have been the primary means of diagnosing these cancers. The histology is assigned to one of three grades ranging from low (grade I), intermediate (grade II), and high (grade III). Histologic grade is currently the key criterion for guiding treatment and determining patient outcome. However, in human medicine and pathology, soft tissue sarcomas are diagnosed with a hybrid approach that involves both histologic features and genetic analysis of the tumor sample. This genetic analysis guides further treatment, aids in developing accurate follow-up information, and has been shown to have a positive effect on patient outcome and survival.

Despite how common soft tissue sarcomas are in the dog, current veterinary care still relies solely on the histologic grade, which is subjective at best, and does not incorporate genetic data into the diagnostic plan. This study will perform transcriptome analysis on 300 canine soft tissue sarcomas in order to establish the transcriptome profile of canine soft tissue sarcoma and correlate this transcriptome to patient follow-up. This will allow for the formation of a hybrid diagnostic approach that will provide more accurate information to inform the prognosis for dogs afflicted with soft tissue sarcoma.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 2783

RESEARCHERS

Andrew Miller, DVM; Cornell University
Amount: $10,000

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. The investigators aim to develop a NGS diagnostic test that can be employed on standard biopsy samples to identify molecular drivers of a patient’s lymphoma (personalized diagnostics), enabling the most appropriate targeted therapy to be selected for that patient. In addition, they aim to determine whether specific mutational profiles within canine lymphoma identified by their NGS panel, are predictive of clinical outcome.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 02441

RESEARCHERS

Nicola Mason, BVetMed, PhD
Trustees of the University of Pennsylvania
Amount: $5,000