Rounding Out National Cancer Research Month

As we round out National Cancer Research Month, we want to highlight the important work being done by FidoCure researchers in comparative oncology. At FidoCure, we’ve pioneered canine cancer research backed by real-world evidence and published our findings in 4 of the most prestigious peer-reviewed scientific journals. Many of these papers are go-to sources for groundbreaking discoveries and advancements in cancer research. Our studies, led by FidoCure’s Head of Veterinary Research, Dr. Lucas Rodrigues, DVM, MS, PhD,  have shed light on the similarities between canine and human cancers, paving the way for novel treatment approaches that could benefit both humans and dogs alike.  Below, you can find the key points of Fidocure’s Nature, Precision Oncology, Elsevier and Veterinary & Comparative Oncology scientific papers.

NPJ Precision Oncology - Analyses of canine cancer mutations and treatment outcomes using real-world clinico-genomics data of 2119 dogs

1. The study analyzed genetic mutations, tumor types, and treatment outcomes for 2119 dogs with spontaneous tumors enrolled in the FidoCure Precision Medicine Platform. Mutations in 48 genes commonly mutated in human cancers were evaluated.
2. Mutations in TP53 and PIK3CA were associated with worse prognosis in the dogs, while mutations in NRAS, ATM, and KIT were associated with better prognosis. These findings showed concordance with human studies for TP53, ATM and KIT mutations.
3. Several targeted therapies designed for humans were associated with positive outcomes when used to treat canine tumors with specific genomic alterations. For example, lapatinib had a positive effect for tumors with BRAF mutations, and trametinib for those with ARID1A mutations.
4. The spontaneous canine tumor model provides a valuable opportunity to identify biomarkers associated with prognosis and treatment response to inform drug development for human precision oncology. The overlap of canine and human cancer mutations associated with therapeutic response can help advance novel treatment strategies.

Nature - Shared hotspot mutations in oncogenes position dogs as an unparalleled comparative model for precision therapeutics

1. This study used targeted sequencing of 56 cancer-associated genes in 109 dogs with splenic hemangiosarcoma (HSA) to identify somatic mutations and germline variants associated with clinical features and outcomes. HSA is an aggressive cancer with poor prognosis in dogs and is a relevant comparative model for human angiosarcoma.
2. The most commonly mutated genes were TP53 (41% of cases), NRAS (18%), and PIK3CA (17%). These frequencies are similar to previous canine HSA studies and human angiosarcoma. Certain mutation patterns suggested convergent effects on key signaling pathways.
3. Survival analysis found that presence of metastasis at diagnosis and germline variants in SETD2 and NOTCH1 were associated with significantly shorter overall survival times. SETD2 variants have been previously linked to cancer progression and poor prognosis in several human cancers.
4. Breed-specific differences were noted, with German Shepherd dogs diagnosed at a younger age and carrying germline CDKN2A variants more frequently than Golden Retrievers and Labrador Retrievers. TP53 and PIK3CA mutations were more common in larger breed dogs.

Elsevier - Precision Medicine in Veterinary Science

1. Precision medicine uses an individual's genomic information to guide prevention, diagnosis, prognosis and treatment of disease. The success of precision medicine in human oncology, based on understanding cancer's genomic heterogeneity and pairing targeted therapies with specific mutations, paves the way for similar approaches in veterinary medicine.
2. Genomic studies have identified mutations and molecular pathways driving canine cancers that are similar to human cancers. This enables translation of knowledge and therapeutic strategies from human to veterinary oncology. Multiple genomic assays for diagnosis, prognosis, treatment selection and monitoring are now commercially available for dogs.
3. Targeted therapies designed for human cancers, such as small molecule inhibitors, are being used in dogs with specific genomic alterations. Early studies show promise for genomically-guided targeted therapies, alone or combined with conventional treatments, in improving outcomes for canine cancer patients.  
4. Precision medicine can be integrated into veterinary oncology practice at multiple points, including using genomic assays for ambiguous diagnoses, prognostication, treatment selection, early cancer screening, and monitoring. As costs decrease, utilization of precision medicine in dogs is expected to expand, improving the knowledge base for clinical decision-making.

Veterinary and Comparative Oncology -Precision Medicine Tools Offer Veterinarians New Hope for Understanding Hemangiosarcoma

1. This study used targeted sequencing of 56 cancer-associated genes in 109 dogs with splenic hemangiosarcoma (HSA) to identify somatic mutations and germline variants associated with clinical features and outcomes. HSA is an aggressive cancer with poor prognosis in dogs and is a relevant comparative model for human angiosarcoma.
2. The most commonly mutated genes were TP53 (41% of cases), NRAS (18%), and PIK3CA (17%). These frequencies are similar to previous canine HSA studies and human angiosarcoma. Certain mutation patterns suggested convergent effects on key signaling pathways.
3. Survival analysis found that presence of metastasis at diagnosis and germline variants in SETD2 and NOTCH1 were associated with significantly shorter overall survival times. SETD2 variants have been previously linked to cancer progression and poor prognosis in several human cancers.
4. Breed-specific differences were noted, with German Shepherd dogs diagnosed at a younger age and carrying germline CDKN2A variants more frequently than Golden Retrievers and Labrador Retrievers. TP53 and PIK3CA mutations were more common in larger breed dogs.

In summary, the remarkable progress being made in comparative oncology highlights the importance of collaboration between veterinary and human medicine, as we work together to combat cancer on all fronts. We look forward to continuing our dedication to cancer research on both ends of the leash.