ASSESSMENT OF RELEVANT MOLECULAR TARGETS WITH THERAPEUTIC SIGNIFICANCE IN CANINE NEOPLASMS.

Cancer is the leading cause of death in companion dogs. The high prevalence and impact on animal welfare, combined with biological and environmental similarities to humans, position canine cancers as valuable models for comparative oncology and translational research. Increasing canine life expectancy and advances in diagnostics have highlighted the need for effective, targeted therapies. While targeted therapies such as tyrosine kinase inhibitors, monoclonal antibodies, antibody-drug conjugates, and immunocytokines have transformed human oncology, their application in veterinary medicine remains limited by scant data on druggable targets in dogs. This doctoral thesis aimed to systematically assess the expression and distribution of selected molecular targets in canine tumors, focusing on aggressive, frequent, or therapeutically challenging neoplasms, and to evaluate their suitability as druggable candidates for targeted therapy and as comparative models for human cancer. The approach combined immunohistochemistry, genetic analyses, and exploratory in vitro studies, focusing on molecules located on neoplastic cells and in the tumor microenvironment: FAP, EDB+FN, KIT (CD117), PDGFR-β, and OXTR. These molecules are involved in tumor progression, stromal remodeling, angiogenesis, and hormonal regulation. Results confirm that canine tumors can harbor multiple therapeutically relevant molecular targets. FAP and EDB+FN are promising targets for payload-delivery and immunocytokine therapies, especially in soft tissue sarcoma, AGASAC, and melanoma. KIT and PDGFR-β show potential for diagnosis and targeted treatment in sarcomas and AGASAC, while OXTR represents an innovative area for further research. The observed heterogeneity of target expression underscores the need for tailored, molecularly guided therapies.