AKC Canine Health Foundation and
Golden Retriever Foundation
Cancer Research Collaborative Project

A Novel Approach for Prevention of Canine Hemangiosarcoma:

The MEDTECH Study (Monitoring for Early Detection and Targeted Elimination of Canine Hemangiosarcoma)

Project Description by Principal Investigator:  Jaime F. Modiano, VMD, PhD        
University of Minnesota, Minneapolis, MN

Project Duration: 36 months

(We are thrilled to announce that the project has been approved by the Canine Health Foundation, and will be starting in January 2016!)
The project will continue the crucial goal to systematically eradicate hemangiosarcoma as a major concern for the Golden Retriever, the Portuguese Water Dog, and the Boxer breeds.

The Problem:  Hemangiosarcoma is the cause of death for one out of every five Golden Retrievers in the United States. Portuguese Water Dogs and Boxers also have an especially high risk for this disease. One feature that makes hemangiosarcoma incurable is the fact that it is almost always detected at a very advanced stage when it is resistant to conventional therapies. This insidious cancer almost always grows out of sight without causing pain or obvious symptoms, so it is diagnosed late in the course of disease or after death.

This status quo is unacceptable.

A method to detect hemangiosarcoma in its earliest stages and an effective mechanism for prevention would be a giant leap forward in the management of this disease.

The Opportunity: Solving the cancer problem is a long-term challenge. However, we believe we have reached a point where we can diagnose hemangiosarcoma in the early stages and treat this disease before it reaches the clinical crisis point. Our goal is to continue development of two technologies that will allow us to achieve this.
First:  a test and patented process to detect hemangiosarcoma cells in the circulation (blood).
Second: a novel drug, heretofore called “bispecific EGF angiotoxin,” or BEAT, which attacks the hemangiosarcoma cancer stem cells that are responsible for establishing and maintaining the disease. BEAT effectively kills the cancer cells or makes the environment inhospitable for their growth. The results from our initial clinical trial have been highly promising.  BEAT acts differently from conventional chemotherapy, so it does not pose the risks that make chemotherapy unacceptable for otherwise healthy patients. At the end of this project, we expect to have created tools to guide further development, licensing and deployment of these paired technologies in the community setting.

Approach: We will recruit cases with a confirmed or presumed diagnosis of hemangiosarcoma and dogs with no evidence of hemangiosarcoma of any age and any breed, as this will accelerate the process of validation.

Summary: The anticipated result will be preliminary tests for detection of circulating hemangiosarcoma cancer stem cells that will be in a “beta”- ready format, along with a safe and reliable treatment option for prevention of disease.

DREAM WITH US! 
Join the Shine On Challenge by making a donation at www.goldenretrieverfoundation.org

1918-G: Discovery of novel protein, blood, and epigenetic biomarkers of lymphoma risk, classification, and prognosis in Golden Retrievers

Investigators/Institutions: Dr. Jeffery N. Bryan, DVM, MS, PhD, of University of Missouri, Columbia; Dr. Anne Avery VDM, PhD, Colorado State University; Dr. Heather Wilson-Robles, DVM, Texas A&M University
Total Grant Amount: $404,813
Grant Period: June 1, 2013 – May 31, 2016

Lymphoma strikes 1 in 8 Golden Retrievers, making them one of the most commonly affected breeds. Dr. Jeffrey Bryan, in collaboration with Dr. Anne Avery (Colorado State University) and Dr. Heather Wilson-Robles (Texas A&M University), will improve diagnostic, classification, and prognostic ability using state of the art technology to characterize the B cell lymphomas of Golden Retrievers. Through joint CHF/GRF funding, these investigators will identify aberrant epigenetic (DNA methylation) changes in lymphoma cells to develop biomarkers of each class of lymphoma, and in turn, identify new therapy targets for affected Golden Retrievers. More significantly, because DNA methylation changes occur so early in the process of cancer formation, these investigators hypothesize that they could serve as biomarkers of risk, allowing medicine or diet to prevent lymphoma in Golden Retrievers before it develops. Finally, they propose to fully phenotype cancer stem cells in lymphoma by surface markers and DNA methylation changes for the purpose of targeting those cells which feed cancer metastasis. Individually each project advances a current frontier of research. By performing them in parallel, the discoveries made in each project can be combined, correlated, and translated into biomarkers of risk, diagnosis, and prognosis to advance the prevention and management of lymphoma in Golden Retrievers. Based on data from other species these investigators expect epigenetic changes to occur across all breeds and anticipate this study will open the door for a deeper understanding of cancer in all dogs.

1889-G: Developing Markers to Diagnose and Guide Cancer Treatment in Golden Retrievers Based on Newly Discovered Heritable and Acquired Mutations
Investigators/Institutions: Dr. Jaime F Modiano, VMD, PhD, of University of Minnesota; Dr. Matthew Breen, PhD, North Carolina State University; Dr. Kerstin Lindblad-Toh, PhD, Broad Institute of MIT and Harvard.
Total Grant Amount: $1,061,137
Grant Period: June 1, 2013 – May 31, 2016

Lymphoma and hemangiosarcoma are major health problems in Golden Retrievers, causing both suffering and premature death. After years of collaboration, Dr. Jaime Modiano (University of Minnesota), Dr. Matthew Breen (North Carolina State University) and Dr. Kerstin Lindblad-Toh (Broad Institute of MIT and Harvard) have made several ground breaking discoveries: 1) they have identified several regions of the genome that contain genetic heritable risk factors for lymphoma and hemangiosarcoma, and 2) they have identified somatic mutations in tumors that occur recurrently in both cancers, some of which are linked to duration of remission when treated with standard of care. These results indicate that a few heritable genetic risk factors account for as much as 50% of the risk for these cancers. These investigators now believe their findings offer the potential to develop strategies for risk assessment in individual dogs, as well as the potential to manage risk across the population as a whole. Further, these inherited risk factors and tumor mutations point to pathways that have been implicated in the pathogenesis of lymphoma and hemangiosarcoma, and thus should inform the development of targeted therapies. Through joint CHF-GRF funding, these investigators will identify precise mutations for the heritable genetic risk factors and will validate markers (mutations) that can be used to determine risk at the heritable loci in a large independent population of Golden Retrievers from the USA and from Europe. Their ultimate goal is to develop robust risk prediction tools, and hopefully, an accompanying DNA test. As has been the case with most genetic-based studies, data are expected to be transferable across all breeds, enabling the future search for cancer risk factors in all dogs to be rapid and focused.