A One Health Approach to Beating Cancer

One Health is a collaborative approach to understanding health and disease in humans, animals, and the environment. When physicians, osteopathic physicians, veterinarians, nurses, and other scientific-health and environmentally related disciplines work together, gains in scientific knowledge occur more rapidly and more efficiently. One Health is a guiding principle in the AKC Canine Health Foundation’s mission to advance the health of all dogs and their owners. Recent discoveries by AKC Canine Health Foundation (CHF) funded researchers demonstrate the power of this approach in fighting cancer, a devastating disease found in humans and dogs.

With rapid advancements in the technology used to study DNA, scientists are investigating the genomics of cancer - describing the structure, function, and editing of genetic material in tumors and normal tissue. Understanding the number, location, and variety of genetic mutations found in various cancers provides insight on how the cancer develops and progresses. Knowledge of how and where these mutations affect cell to cell communications that facilitate cancer indicates potential treatment targets. If we block the effects of a mutation, we may be able to block cancer progression. Some promising examples from CHF-funded research include the following:

• Bladder cancer – Invasive urothelial carcinoma represents approximately 25% of human bladder cancers and is the most common bladder cancer in dogs. The clinical presentation, age of onset, and response to treatment are similar in both species. Investigators identified two clusters of dysregulated genes in canine bladder tumors that correspond with similar mutations in human bladder tumors.
  Grant 00754A: Mapping of the Gene for Transitional Cell Carcinoma in the Scottish Terrier & West Highland White Terrier
  Grant 01336A: Finding the Mutations that Increase Susceptibility to Transitional Cell Carcinoma in the Scottish Terrier, West Highland Terrier, and Shetland Sheepdog
  Grant 01577: Identifying the Genes Conferring Risk for Transitional Cell Carcinoma

• Histiocytic Sarcoma – Histiocytic sarcoma is a rare, aggressive, and varied cancer in humans – all properties that make it difficult to study. Its prevalence in several dog breeds such as Bernese Mountain Dogs and Flat-Coated Retrievers provides a better opportunity to understand the molecular mechanisms of this disease. Investigators found mutations that affect one specific cell signaling pathway in the majority of visceral disseminated canine histiocytic sarcoma cases, the most aggressive form of this cancer in dogs. That same mutation was found in several human patients.
  Grant 02446: Development of Genetic Biomarkers to Improve Diagnosis and Treatment of Canine Histiocytic Sarcoma

• Osteosarcoma – Osteosarcoma is the most common bone cancer in dogs and is similar to pediatric bone cancer in humans. A cell to cell communication pathway known as the Hedgehog cell signaling pathway normally regulates cell growth and differentiation in human bones. When that regulation is disrupted, a cascade of events occurs resulting in the activation of genes that cause cancer growth. Investigation of the Hedgehog cell signaling pathway in canine osteosarcoma showed variable similarities, indicating that this pathway plays a role in canine bone cancer, but not exactly the same role as in human bone cancer.
  2016 Clinician-Scientist Fellowship, Cornell University

• Hemangiosarcoma – Human angiosarcoma is another rare, aggressive, and varied human cancer that affects blood vessel cells. The canine equivalent is hemangiosarcoma, a devastating cancer that affects the spleen, heart, and skin of dogs. Investigators identified mutations in one tumor suppressor gene and two tumor promoting genes in canine hemangiosarcoma tissues that resemble mutations seen in human angiosarcoma tumors of the breast and viscera (internal organs).
  Grant 01131: Genetic Background and the Angiogenic Phenotype in Cancer

Understanding the similarities and differences in tumor biology between humans and dogs is an important step in helping both species fight cancer. Naturally occurring cancer in dogs is often a good model for human cancer because disease development and response to treatment can be similar in both species. Exploring the genetic characteristics of various cancers is critical to refine our knowledge of the disease and focus our treatment efforts. The AKC Canine Health Foundation and its donors are committed to this One Health approach to beating cancer, so that both dogs and humans can live longer, healthier lives.

Explore our Research Grants Portfolio at akcchf.org/portfolio for studies in oncology and other health concerns that have One Health implications.

References:

1. Parker, H. G., Dhawan, D., Harris, A. C., Ramos-Vara, J. A., Davis, B. W., Knapp, D. W., & Ostrander, E. A. (2020). RNAseq expression patterns of canine invasive urothelial carcinoma reveal two distinct tumor clusters and shared regions of dysregulation with human bladder tumors. BMC Cancer, 20(251). doi.org/10.1186/s12885-020-06737-0
2. Hédan, B., Rault, M., Abadie, J., Ulvé, R., Botherel, N., Devauchelle, P., Copie‐Bergman, C., Cadieu, E., Parrens, M., Alten, J., Zalcman, E. L., Cario, G., Damaj, G., Mokhtari, K., Loarer, F. L., Coulomb‐Lhermine, A., Derrien, T., Hitte, C., Bachelot, L., … André, C. (2020). PTPN11 mutations in canine and human disseminated histiocytic sarcoma. International Journal of Cancer. doi.org/10.1002/ijc.32991
3. Baldanza VE, Rogic A, Yan W, Levine CB, Levine RA, Miller AD, et al. (2020) Evaluation of canonical Hedgehog signaling pathway inhibition in canine osteosarcoma. PLoS ONE 15(4): e0231762. doi.org/10.1371/journal.pone.0231762
4. Megquier, K., Turner-Maier, J., Swofford, R., Kim, J.-H., Sarver, A. L., Wang, C., … Lindblad-Toh, K. (2019). Comparative Genomics Reveals Shared Mutational Landscape in Canine Hemangiosarcoma and Human Angiosarcoma. Molecular Cancer Research, 17(12), 2410–2421. doi.org/10.1158/1541-7786.MCR-19-0221