Combining Therapies to Improve Osteosarcoma Treatment

Posted on by Crystal Smith

SUMMARY: Researchers will study whether a combination of oral medication and new tumor vaccine provide survival benefit for dogs diagnosed with osteosarcoma.

THE PROBLEM: Osteosarcoma (OS) is the most common bone cancer in dogs, affecting the long bones of mostly large and giant breeds of dog. The standard treatment for OS is amputation of the limb followed by a course of chemotherapy. Despite this treatment, half of dogs develop spread of their cancer at 6 months after amputation, and half of dogs do not live beyond 300 days; only 25% of dogs live to 2 years. This is because once OS has spread, it is extremely resistant to treatment, with less than 10% of dogs responding to any type of therapy. No improvements for the care of dogs with OS have happened in over 30 years, despite many studies using combinations of chemotherapy and immune-based approaches.

THE PROJECT: It is now known that OS cells prevent the immune system from killing them by creating an environment around the tumor that blocks the ability of immune cells to work. To address this, the research team has combined three oral medications that help to activate immune cells in the tumor and restore immune function. In a recent study of dogs with OS spread to the lungs, 30% of dogs responded to the treatment, with one dog cured of disease. Also, another 40% of dogs had their disease stop growing, more than doubling survival time from an average of 60-90 days after the diagnosis of OS spread to over 150 days. The purpose of this study is to improve on this oral therapy by adding a new OS tumor vaccine. The vaccine uses a special formula to stimulate the immune system. This vaccine formula was found to be safe and was able to partially shrink tumors in the setting of canine brain cancer. The team believes that this combined therapy will improve the response in dogs that already have spread of OS to the lungs and will also improve their survival.

POTENTIAL IMPACT: If the study results are positive, the treatment approach of combining oral medications with a tumor vaccine could become widely available to dogs with OS. Lastly, because the vaccine can be made to be specific for different kinds of cancer using cancer cell lines rather than tissues from a biopsy, this approach has the potential to treat dogs beyond those with OS.

Co-sponsored with the Morris Animal Foundation, Grant Number: 25CAINEI-0016

RESEARCHERS

Cheryl London, DVM, PhD, Tufts University, and Steven Dow, DVM, PhD, Colorado State University,

Amount: $10,000

Mitochondrial Dysfunction and mtDNA Mutations in Canine Hemangiosarcoma: Novel Biomarkers for Early Diagnosis and Personalized Therapy

Posted on by Crystal Smith

SUMMARY: Researchers will study if dysfunction of the mitochondria, the cell’s “powerhouses,” are drivers of tumor aggressiveness.

THE PROBLEM: Hemangiosarcoma is a highly aggressive and rapidly progressing cancer of dogs. Hemangiosarcoma is usually diagnosed when the tumor is in an advanced stage. Nearly 90% of all dogs die within the first year of diagnosis, and long-term survival is rare. New treatments are desperately needed.

THE PROJECT: Recent findings in human oncology strongly indicate that mitochondrial dysfunction serves as a crucial driver of cancer progression, metastasis, and treatment resistance. Unfortunately, there is a lack of information about how mitochondrial dysfunction could influence cancer progression dogs. This innovative study aims to address this critical gap by investigating mitochondrial dysfunction and associated mitochondrial DNA (mtDNA) mutations within canine HSA tumors. Utilizing advanced techniques, including spatial transcriptomics, cutting-edge mtDNA sequencing and comprehensive bioenergetic profiling, this study will identify regions of tumors exhibiting severe mitochondrial impairment and hyperactivation. Identifying region-specific mitochondrial dysfunction is vital, as it reveals different metabolic and genetic signatures directly linked to tumor aggressiveness. We hypothesize that region-specific mitochondrial dysfunction drives tumor aggressiveness through oxidative stress, mtDNA mutations, and synergy with oncogenic mutations.

POTENTIAL IMPACT: Identifying mitochondrial molecular signatures could lead to non-invasive blood-based biomarkers, enabling earlier detection and personalized therapies, offering new hope for veterinarians, pet owners, and affected dogs alike.

Co-sponsored with the Morris Animal Foundation, Grant Number: 26CAANFT-0005

RESEARCHERS

Krysztof Marycz, Ph.D, CVT; International Institute of Translational Medicine (MIMT)

Amount: $10,000

Engineering a monoclonal antibody therapy for canine mast cell tumors

Posted on by Janet Boyd

Mast cell tumors (MCT) are the most common skin tumors in dogs. MCTs can vary in their growth from slow-growing to highly aggressive tumors, and treatment options are often limited, especially for tumors that have spread or can’t be removed. Chemotherapy is sometimes used, but has side effects. Despite treatment, most dogs eventually succumb to disease within a year of diagnosis. This highlights the need for more effective and precise therapy.

This study focuses on developing a new treatment using monoclonal antibodies (mAbs). mAbs are already used to treat many human cancers. But in veterinary medicine, they are still new and not widely available. The antibodies are designed to target the protein KIT on mast cells. KIT is present on mast cells but not on other immune cells. By targeting KIT, the antibodies can precisely attack cancer cells while leaving healthy cells unharmed. Researchers will evaluate how well these mAbs bind to KIT and kill cancer cells. The mAbs will be engineered to work more effective for dogs by designing them to look like natural canine antibodies.

The research goal is to develop a safe and effective therapy for dog mast cell cancer that can also serve as a model for treating similar conditions in other species that suffer from mast cell diseases, including humans and cats.

Co-sponsored with the Morris Animal Foundation, Grant Number: 26CAANFT-0005

RESEARCHERS

Marietta M Ravesloot-Chavez, PhD; University of California Davis

Amount: $15,000

Studying Hemangiosarcoma Subtypes and Treatment Response

Posted on by Crystal Smith

SUMMARY: Researchers are studying if hemangiosarcoma subtypes influence how affected dogs respond to treatment – a step toward precision medicine for these  patients.

DESCRIPTION: Research suggests that hemangiosarcoma, a deadly cancer in dogs, is not one disease but made up of many different subtypes. The team found that dogs with one type of HSA are more likely to live longer than dogs that have a different  type of HSA. This may explain why current treatments fail to help most dogs with HSA live longer despite aggressive care. To address this issue, researchers will identify the HSA type or signature in tumors from dogs that have lived longer than other dog patients with HSA. The team is using data from a study in progress to inform their evaluation of archived tissues to assess prevalence and survival. They hope their  findings will help uncover the best treatment options for individual dogs with specific types of HSA and improve outcomes for this challenging canine cancer.

POTENTIAL IMPACT: If the team is successful, their findings could have a major impact  on how HSA is treated in dogs as well as provide information on long-term prognosis based on subtype. These results could help both veterinarians and pet parents make more informed decisions for dogs diagnosed with this terrible cancer.

Co-sponsored with the Morris Animal Foundation, Grant Number: D24CA-535

RESEARCHERS

Erin Dickerson, PhD; University of Minnesota

Amount: $10,000

Discovery of public tumorspecific neoantigens (pTSNAs) and pTSNAreactive T cells arisen from hotspot mutations in canine hemangiosarcoma

Posted on by PWDF Dev

Researchers will build on their discovery of “hotspot” mutations (tumor mutations shared between patients with the same cancer) to see if they can identify public tumor-specific neoantigens (pTSNAs) that are thought to play a role in immune response to cancer. Researchers hope findings will be a step toward a new immunotherapy that can be used in many different dogs suffering from hemangiosarcoma.

A no cost extension has been approved by MAF (April 2026) as a result of the following request of the researcher:

We request a one-year No-Cost Extension (NCE), extending the project end date to March 31, 2027, to investigate longitudinal T cell receptor (TCR) repertoire dynamics using yearly blood samples from healthy dogs and dogs that developed hemangiosarcoma, collected through the Golden Retriever Lifetime Study (GRLS). This work will be performed using our newly developed, highly innovative, dog[1]specific, rhPCR-based TCR-seq protocol (Aim 2). The study will provide novel insights into the role of TCR repertoire aging in hemangiosarcoma development and may identify potential biomarkers for disease detection and treatment response through liquid biopsy.

Our sample request has been approved by the GRLS committee, and we are currently in the process of selecting and receiving the samples. We will begin rhPCR TCR-seq analysis immediately upon sample arrival.

During the NCE period, we will also complete three manuscript submissions to peer-reviewed journals reporting our findings: 1) MHC-II genotyping results (Aim 1), 2) neoantigen discovery results (Aims 1 and 2), and 3) canine TCR repertoire characterization (Aim 2).

Co-sponsored with the Morris Animal Foundation, Grant Number: D24CA-536

RESEARCHERS

Shaying Zhao, PhD, University of Georgia
Amount: $10,000

Using a heritable immunostimulatory bacterium to block heartworm transmission by mosquitoes

Posted on by PWDF Dev

Summary: Researchers will investigate the use of a bacteria to help block transmission of heartworm parasites by mosquitoes.

Description: More than 150,000 cases of canine heartworm disease are reported annually in the United States alone. Monthly preventive treatments for dogs have been widely available since the mid-19805. However, drug-resistant strains are on the rise, highlighting the need for novel disease control strategies. Researchers will investigate how infection by certain bacteria decreases the capacity of mosquitoes to transmit infectious larvae of Dirofilaria immitis, the agent of heartworm disease. Bacteria-infected mosquitoes (and control groups) will be exposed to both drug-sensitive and drug-resistant parasites. The team hopes findings will provide a new approach to block the spread of the heartworm disease by targeting parasites in their mosquito host.

Co-sponsored with the Morris Animal Foundation, Grant Number: D22CA·015

RESEARCHERS

Michael Povelones; University of Pennsylvania
Amount: $10,000

Pathology Residency Training Program to support the Morris Animal Foundation Golden Retriever Lifetime Study

Posted on by Janet Boyd

This grant supports the advanced training of two aspiring veterinary pathologists who will assist with the analysis of tissue samples collected from dogs enrolled in Morris Animal Foundation’s Golden Retriever Lifetime Study.

Highly trained investigators are vital to advancing the health and welfare of animals. Morris Animal Foundation is funding the training of two new veterinary pathologists to work with the Golden Retriever Lifetime Study research team. Under the mentorship of the study’s veterinary leadership team, the selected pathology residents will help examine submitted tissue samples from study participants in order to provide consistency in diagnosis of diseases, including cancer, as well as assist with advanced pathology diagnostics and reporting as needed.

Co-sponsored with the Morris Animal Foundation, Grant Number: D16CA-001

RESEARCHERS

EJ Ehrhart, DVM, PhD, DACVP, Colorado State University
Amount: $10,000

Understanding the Relationship between Intestinal Bacteria and Inflammatory Bowel Disease (IBD)

Posted on by Janet Boyd

Scientific Title: Tackling the Canine Microbiome in Chronic Enteropathy: Characterizing the Functionally Significant Changes that Occur with Remission of Disease

Summary: Researchers are looking at changes in gut bacteria that stimulate the immune system in dogs with inflammatory bowel disease to help identify novel ways to diagnose and treat this disease.

Description: Inflammatory bowel disease (IBD) is a common disease of dogs, causing vomiting, diarrhea and weight loss. Some studies suggest that specific intestinal microbiota can drive or exacerbate intestinal inflammation, but this mechanism has not been well studied in dogs. Researchers will assess and track certain bacteria, known to interact directly with the gut immune system, in stool samples of dogs with inflammatory bowel disease. Data will be collected during treatment until the dogs gain remission. Findings will validate if these bacteria are functionally important to the disease process, and how treatment modifies the gut bacteria.

This new information will lead to a better understanding of how the gut microbiome can be manipulated in dogs with IBD and may reduce the need to directly biopsy the intestine to establish a definitive diagnosis of this condition.

Co-sponsored with the Morris Animal Foundation, Grant Number: D18CA-045

RESEARCHERS

Dr. Caroline S Mansfield
The University of Melbourne, Australia
Amount: $10,000

Investigating Cancers and Exposure to Environmental Chemicals

Posted on by Janet Boyd

Scientific Title: Detoxification of Environmental Carcinogens by Glutathione-Stransferases in Dogs

Summary: Researchers will find out how the dog’s body breaks down common environmental chemicals that have been linked to cancers in humans.

Description: When dogs or humans are exposed to toxic chemicals in the environment, they use glutathione-S-transferase (GST) enzymes to break down and neutralize those chemicals. When GST enzymes are not working, toxic chemicals sometimes lead to cancers such as lymphoma or bladder cancer. Researchers will test how well four major GST dog enzymes can neutralize several common environmental chemicals, including those found in tobacco smoke and yard products.

Results will provide a clearer understanding of whether individual dogs with low-acting GSTs may be sensitive to specific chemicals and, as a result, more susceptible to developing environmentally associated cancers.

Co-sponsored with the Morris Animal Foundation, Grant Number: D18CA-070

RESEARCHERS

Dr. Lauren A Trepanier
University of Wisconsin-Madison
Amount: $10,000

Measuring Chemotherapy Drug Resistance in Dogs with T-cell Lymphoma

Posted on by PWDF Admin

Quantitative Assessment of Minimal Residual Disease Kinetics during CHOP Chemotherapy of Canine T-cell Lymphoma via Next-Generation TCRVß Sequencing

Human cancer treatment is becoming more and more tailored to each individual case and tumor characteristics. This study will be conducted by researchers at North Carolina State University and will follow a small number of cells that evade chemotherapy agents, providing information on the effectiveness of particular agents against T-cell lymphoma. The data from this study will be used to personalize treatment protocols for dogs on an individual basis in hopes of improving outcomes, survival rates, and quality of life.

Description: Since the use of combination chemotherapy was first reported in 1968, little progress has been made in improving the survival of dogs with T-cell lymphoma. Effectively monitoring chemosensitivity – the number of tumor cells killed by chemotherapy– of individual lymphoma cells exposed to multiple agents over many treatments remains a challenge. Following the small numbers of cells that evade chemotherapy would provide information on the effectiveness of a particular chemotherapy agent.

In this clinical trial, researchers will use state-of-the-art DNA technology to measure changes in this small population of resistant cancerous T-cells in client-owned dogs with lymphoma. Data will be used to personalize treatment protocols for individual dogs in hope of improving survival and quality of life.

Co-sponsored with the Morris Animal Foundation, Grant Number: D16CA-056

RESEARCHERS

Dr. Paul R. Hess, DVM, PhD
North Carolina State University
Amount: $10,000