Comparative pathophysiology and molecular insights into cutaneous and non-cutaneous canine skin cancers: focus on melanoma, mast cell tumors, and squamous cell carcinoma.

Skin cancer is one of the most frequently diagnosed neoplasms in dogs, encompassing a range of malignancies with significant clinical implications. Among them, mast cell tumors (MCTs), melanomas, and squamous cell carcinomas (SCCs) signify the most common and clinically relevant types, each posing distinct therapeutic challenges and exhibiting pathophysiological mechanisms. MCTs, accounting for approximately 21% of canine skin tumors, are often driven by mutations in the KIT proto-oncogene, leading to an uncontrolled proliferation of mast cells. Melanomas, while typically benign in cutaneous forms, exhibit aggressive behavior in oral and digital locations, with BRAF and NRAS mutations playing an integral role in tumor growth. Furthermore, SCCs, primarily associated with chronic ultraviolet (UV) radiation exposure, demonstrate significant genomic modifications, including mutations in TP53 and increased expression of COX-2, resulting in carcinogenesis. Accurate diagnosis of these tumors significantly relies on cytology, histopathology, and immunohistochemical markers. Moreover, advanced imaging techniques such as computed tomography (CT) and positron emission tomography (PET) can potentially enhance staging and prognostication. Treatment modalities vary based on tumor type and stage, including surgical excision, radiation therapy, chemotherapy, and emerging targeted therapies. Tyrosine kinase inhibitors (TKIs), such as toceranib phosphate (Palladia) and masitinib, have demonstrated efficacy in MCTs. Likewise, immunotherapies, including the Oncept melanoma vaccine and checkpoint inhibitors, offer novel therapeutic avenues. Comparative oncology continues to underscore molecular similarities between canine and human skin cancers, advancing translational research and developing precision medicine techniques in veterinary oncology. This review comprehensively synthesizes state-of-the-art literature on canine skin cancer, addressing pathophysiological mechanisms, diagnostic advancements, and emerging therapeutic strategies. In addition, this review aims to improve early detection, treatment outcomes, and enduring prognosis for affected canines by integrating recent findings into molecular oncology and comparative medicine.