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

A combined sensor approach to examine volatile organic compounds as potential markers of canine hemangiosarcoma

Posted on by Crystal Smith

SUMMARY: Researchers will determine the volatile organic compound (VOC) profile of hemangiosarcoma using bio-detection dogs as a step toward a diagnostic test for the disease.

THE PROBLEM: Canine hemangiosarcoma (HSA) is a deadly cancer in dogs that is often diagnosed too late for effective treatment, making early detection crucial. Despite years of research, early detection of the disease remains elusive, and new approaches are needed.

THE PROJECT: This study aims to take the next step toward developing a simple, non-invasive test for HSA by identifying a specific odor fingerprint linked to the disease. Characterizing the VOC profile using analytical techniques is a vital step, providing foundational data that can benefit researchers across various disciplines. Trained bio-detection dogs have been able to correctly identify canine HSA blood serum samples from line-ups which included serum from healthy dogs and dogs unwell with other conditions, with an average accuracy of 71%. Building on this finding, the proposed study will chemically analyze the volatile organic compounds (VOCs), in the blood of dogs with confirmed HSA, healthy dogs, and dogs with other illnesses. These VOCs will be recreated as synthetic odors and presented to the trained dogs to help confirm which parts of the odor are most important for detecting the disease. While we do not anticipate the bio-detection dogs as part of the final diagnostic test, they serve as critical biosensors in this research. Their ability to detect specific odors present in HSA will help us define the VOC signature of the disease.

POTENTIAL IMPACT: This results from this study will inform the development of future non-invasive tests, like a blood test, that could be used in regular screenings for at-risk dogs, enabling earlier detection and improving survival rates.

Co-sponsored with the Morris Animal Foundation, Grant Number: 25CAINEI-0038

RESEARCHERS

Cynthia Otto, DVM, PhD,; University of Pennsylvania

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

Building a Portuguese Water Dog Reference Genome to Unlock Breed-Specific Health Insights

Posted on by Janet Boyd

The Portuguese Water Dog Foundation is very excited to join with Drs. Jaime Modiano VMD, PhD and Steven Friedenberg DVM, PhD, DACVECC in a project to improve the lives and well-being of PWDs. The team of Drs. Modiano and Friedenberg will lead a project creating a reference genome specific to PWDs, which will improve our ability to identify genetic drivers of common inherited disorders in the PWD. This project is fully funded by your donations to the PWD Foundation. Once completed, this high-quality reference genome will be made available to the public, allowing researchers from around the world to access this cutting-edge resource that will enhance the breed’s welfare.

Background of Canine Genome

Both Addison’s disease and hemangiosarcoma impose serious health burdens on Portuguese Water Dogs (PWDs). Other conditions – for example hip dysplasia, dilated cardiomyopathy, inflammatory bowel disease, and hypothyroidism – also disproportionately affect the breed. Efforts to pinpoint the genetic drivers of these disorders have been limited by reliance on canine reference genomes built from other dog breeds, such as the Boxer (CanFam 3.0) and German Shepherd (CanFam 4.0), which miss PWD-specific variation, particularly in complex or repetitive regions of the genome. Human genome studies have shown that relying on a single reference can omit up to 10% of a species’ genetic content – hundreds of millions of bases and the majority of structural variants – highlighting just how much PWD-specific information may be lost without a dedicated genome assembly.

How This Project Will Make a Difference

This project will generate a high-quality, telomere-to-telomere reference genome combining the latest technologies, to produce a PWD genome assembly of unprecedented accuracy and completeness. Crucially, this assembly will be released publicly so that researchers everywhere can align existing and future PWD sequencing data directly to the correct reference. Additionally, this assembly will enable researchers to compare PWD genomes with those of other breeds – unlocking insights into inherited variation that governs morphology, disease risk, and longevity.

This breed-specific framework will immediately accelerate discovery of genetic variants underlying Addison’s, hemangiosarcoma, and the full spectrum of PWD-predisposed conditions. Existing whole-genome and targeted sequencing datasets can be reanalyzed at once, and all future studies will benefit from a precise, breed-specific scaffold for variant calling, functional annotation, and the development of diagnostic tests. By funding a PWD reference genome, the Foundation will help create a lasting, community-wide resource that transforms research, informs breeding decisions, and ultimately improves the healthspan of PWDs.

The Team Behind the Project

The research team will be co-led by Dr. Steven Friedenberg, DVM, PhD, and Dr. Jaime Modiano, VMD, PhD. Together, Drs. Friedenberg and Modiano are uniquely positioned to complete this work because of their deep knowledge of PWDs and complementary skill set. Dr. Friedenberg brings years of experience studying Addison’s disease in Portuguese Water Dogs along with deep bioinformatics expertise, while Dr. Modiano, a world-renowned cancer biologist, has spearheaded hemangiosarcoma research in the breed. Bioinformatics analyses will be driven by Dr. Friedenberg’s graduate student Hayden Hamsher, who already has two years of pipeline development experience, and the project will benefit from the guidance of Dr. Jonah Cullen, whose postdoctoral work on the horse pangenome will provide invaluable genome assembly knowledge. They have also enlisted collaborators at UC Santa Cruz, the University of Washington, and the BC Cancer Research Centre – each contributing specialized expertise in long-read sequencing, Omni-C scaffolding, and Strand-seq methodologies. Together, this multidisciplinary team combines breed-specific veterinary insight, advanced computational skills, and world-class sequencing know-how to ensure the success of the PWD reference genome.

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

Advancing Canine Health: Liquid Biopsy for Early Relapse Detection and Improved Treatment of Mast Cell Tumors

Posted on by Crystal Smith

Mast cell tumor (MCT) is the most common malignant canine skin tumor, accounting for 16-21% of all skin tumors. All breeds can develop MCTs, but many purebreds (e.g., Boxers, Boston Terriers) are predisposed. Clinical management is challenging due to  unpredictable biological behavior and inaccurate biomarkers. While surgery is the  primary treatment, many dogs develop resistance to chemotherapy within months.

This study aims to develop a non-invasive “liquid biopsy” that uses blood sampling to  detect early disease progression and therapy resistance. Next-generation sequencing  (NGS) will measure tumor burden through circulating DNA, potentially revolutionizing  how we monitor these patients, improving their quality of life, and significantly  impacting veterinary oncology.

Relevance to PWDs:
All breeds can develop MCTs, including PWDs. This research offers significant  potential benefits by developing a non-invasive blood test that could detect relapse  earlier, improve treatment outcomes, and reduce the need for sedation or anesthesia  during monitoring. The non-invasive monitoring method being developed  would benefit any breed diagnosed with this common cancer.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 03368

RESEARCHERS

Paulo Vilar Saavedra, DVM, MS; University of Florida

Amount: $5,000

Identification of Bartonella henselae Immunodominant Epitopes for Diagnosis and Prevention of Canine Bartonelloses

Posted on by Crystal Smith

Bartonella species are associated with severe diseases in dogs, including endocarditis, myocarditis, hepatitis, lymphadenitis, hemangiosarcoma, vasculitis, arthritis, uveitis,  meningitis, and others.

Despite diagnostic advances, current tests lack sensitivity. Bartonella infections pose a serious threat to dogs and public health due to potential transmission to humans. This study will identify Bartonella henselae B-cell and T-cell epitopes (parts of proteins recognized by the immune system) using immunoproteomic approaches. The results  will help develop a reliable ELISA diagnostic test and provide insights into proteins  that should be targeted in future vaccines to prevent Bartonella infection in dogs.

Relevance to PWDs: As with the companion Bartonella study, improved diagnostics  and potential preventive measures would benefit all breeds, especially those involved  in outdoor sports and activities.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 03337

RESEARCHERS

Edward Breitschwerdt, DVM, DACVIM; North Carolina State University

Amount: $5,000

Towards Curative Outcomes in Canine Hemangiosarcoma

Posted on by Crystal Smith

This nationwide clinical trial aims to achieve curative outcomes for 400 dogs with splenic hemangiosarcoma—a highly aggressive cancer that disproportionately affects  older, large breed dogs. Despite aggressive treatment, more than 50% of affected  dogs die within 6 months due to metastatic spread. The research will leverage  genomic insights to: (1) identify molecular biomarkers for prognosis; (2) define  genomic subgroups that may benefit from specific anticancer drugs; and (3) develop  new therapeutic approaches to prevent cancer spread. This approach follows the  roadmap used in transforming childhood leukemia from a fatal diagnosis to a commonly cured disease.

Relevance to PWDs: PWDs are at risk for hemangiosarcoma. This study could  transform treatment approaches for this devastating disease that currently has poor outcomes. The innovative approach could lead to personalized treatment protocols  and potentially curative therapies for affected dogs.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 02946

RESEARCHERS

Chand Khanna, DVM, PhD; Ethos Discovery

Amount: $10,000

Artificial Intelligence-based Image Analysis of Lymph Node Mast Cell Burden in Canine Cutaneous Mast Cell

Posted on by Crystal Smith

Canine mast cell disease is one of the most common cancers in dogs. These tumors can be aggressive, with local recurrence, metastasis, and disease progression resulting in death. Lymph nodes are a major site of metastasis for canine mast cell tumors, and lymph nodes are routinely removed and evaluated for metastasis as part of the clinical workup in dogs with this disease.

The research team aims to use deep-learning based digital image analysis to evaluate lymph nodes in dogs with cutaneous mast cell tumors for specific microscopic features associated with the risk of disease progression and death. These criteria can then be evaluated in dogs with mast cell disease, providing clinicians with additional prognostic information and allowing for more guided and meaningful therapy.

Co-sponsored with the AKC Canine Health Foundation, Grant Number: 03282

RESEARCHERS

Ryan Jennings, DVM, PhD; Ohio State University

Amount: $5,000