Original Project Description:
High-grade B cell lymphoma is a cancer frequently diagnosed in older dogs, with Golden Retrievers and Bernese Mountain Dogs being particularly predisposed. Standard veterinary care involves chemotherapy and while patients initially respond well, the disease proves to be fatal for most dogs diagnosed. In human medicine, chimeric antigen receptor (CAR) T cell therapy, in which the patient’s T lymphocytes are engineered to target and kill their cancer, has been remarkably successful for treating B cell lymphoma. However, a significant number of patients become resistant to this therapy due to loss of target antigen on their cancer cells. To overcome this, next-generation tandem CAR T cells were designed to kill cancer cells by recognizing two separate targets, thereby reducing the ability of cancer cells to escape treatment, and greatly improving the outlook for human patients.
Research Update CHF 02772 FINAL: Identifying Early Stage Ultra-rare Mutations as Predictive Biomarkers of Lymphoma in High-risk versus Low-risk Breeds Within the Dog Aging Project
The primary goal of this project is to test the hypothesis that breeds vary in risk of lymphoma due, at least in part, to breed-specific variation in rates of mutation in genes relevant to lymphoma. To test this hypotheses, we needed to gather blood samples from breeds at high risk and low risk of lymphoma, and from individuals of different ages within those breeds. We would then measure the frequency of rare mutations in several genes, and ask if this frequency is higher in breeds at relatively high risk of lymphoma. Continue reading “Research Update CHF 02772 FINAL: Identifying Early Stage Ultra-rare Mutations as Predictive Biomarkers of Lymphoma in High-risk versus Low-risk Breeds Within the Dog Aging Project”
Research Update Final 02309-T: Targeting the Cancer Epigenome: The Effect of Specific Histone Lysine Methyltransferase Inhibition in Canine B-Cell Lymphoma
Lymphoma, particularly the large, B-cell subtype, is one of the most common malignancies in dogs. Canine lymphoma can be treated, but it is rarely cured. Novel therapeutic strategies are necessary to improve outcomes in dogs diagnosed with lymphoma. Continue reading “Research Update Final 02309-T: Targeting the Cancer Epigenome: The Effect of Specific Histone Lysine Methyltransferase Inhibition in Canine B-Cell Lymphoma”
Research Update CHF 02502 EY3: Precision Medicine for Canine Lymphoma
We have successfully developed a canine cancer gene panel that we have called the Canine Oncopanel, using cutting-edge, next-generation sequencing technology (NGS). The Canine Oncopanel allows sequencing of 283 cancer-related genes and detection of mutations within these genes that may drive the tumor cells to proliferate and survive. The canine oncopanel sequences a total target region that equates to ~3% of the canine genome. Analyzing the genomic composition of this broad target region allows evaluation of common genomic alterations that can lead to the development of cancer. The Canine Oncopanel is suitable to map mutation profiles and identify driver mechanisms in both common and rare canine cancers to provide a better understanding of the tumor genome and its biology.
Continue reading “Research Update CHF 02502 EY3: Precision Medicine for Canine Lymphoma”
Research Update MAF D16CA-056 Final: Measuring Chemotherapy Drug Resistance in Dogs with T-cell Lymphoma
RESULTS: New Technology Helps Detect Small Amounts of Drug-Resistant Cancer Cells in Dogs with T-cell Lymphoma.
Morris Animal Foundation-funded researchers from North Carolina State University used state-of-the-art DNA technology to help detect small amounts of drug-resistant cancer cells that persist after treatment in dogs with T-cell lymphoma (minimal residual disease, MRD). Accurately monitoring MRD could provide a fuller picture of the effectiveness of different drugs and improve treatment success, quality of life and survival for these patients. Continue reading “Research Update MAF D16CA-056 Final: Measuring Chemotherapy Drug Resistance in Dogs with T-cell Lymphoma”
Research Update CHF 02317 Final: The Role of Complex Translocations Associated with TP53 Somatic Mutations for Aiding Prognosis of Canine Diffuse Large B-Cell Lymphoma
This study involved the evaluation of canine lymphoma biopsy specimens for the presence of tumor-associated abnormalities associated with four key cancer-associated genes (MYC, BCL6, BCL2, and TP53). In a subset of human lymphoma patients, cancer cells show structural rearrangements of MYC, BCL2, and/or BCL6, meaning that the normal organization of the gene has become disrupted in the tumor. Human lymphomas also frequently show DNA sequence mutations in the TP53 tumor suppressor gene. The presence of these abnormalities, alone and particular in combination, has been shown to be predictive of a poor response to standard treatment modalities in human lymphoma patients, and provides powerful opportunities to predict prognosis in newly diagnosed patients. Continue reading “Research Update CHF 02317 Final: The Role of Complex Translocations Associated with TP53 Somatic Mutations for Aiding Prognosis of Canine Diffuse Large B-Cell Lymphoma”
Research Update CHF 02502 MY3: Precision Medicine for Canine Lymphoma
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. Continue reading “Research Update CHF 02502 MY3: Precision Medicine for Canine Lymphoma”
Research Update Mid-year 4 02309-T: Targeting the Cancer Epigenome: The Effect of Specific Histone Lysine Methyltransferase Inhibition in Canine B-Cell Lymphoma
Lymphoma, particularly the large, B-cell subtype, is one of the most common malignancies in dogs. Canine lymphoma can be treated, but it is rarely cured. Novel therapeutic strategies are necessary to improve outcomes in dogs diagnosed with lymphoma. Recently, advances in the understanding of human lymphomas have focused on the area of epigenetics.
Research Update End-year 2 CHF 02502: Precision Medicine for Canine Lymphoma
This AKC-CHF sponsored award supported the successful development of a comprehensive canine tumor sequencing panel (“canine oncopanel”) using cutting-edge, next-generation sequencing technology.
Continue reading “Research Update End-year 2 CHF 02502: Precision Medicine for Canine Lymphoma”
Research Update CHF Grant 02317 Update End-Year 3: The Role of Complex Translocations Associated with TP53 Somatic Mutations for Aiding Prognosis of Canine Diffuse Large B-Cell Lymphoma
Update on treatment of B-cell lymphoma from Dr Breen.