Naturally Occurring Canine Hemangiosarcoma as a Translational Model for Angiosarcoma

Angiosarcomas are malignant vascular cancers that are rare in humans, accounting for 1-2% of all sarcomas. These aggressive malignancies have a high metastatic propensity, leading to a poor prognosis. No effective targeted therapy for angiosarcomas has been established yet, with previous studies showing unfavorable clinical benefits. The rarity of angiosarcoma and its underrepresentation in cancer research underscore the urgent need for foundational studies and the development of reliable translational animal models. A major challenge in this field is the limited availability of research tools and faithful animal models for studying rare human cancers. This limitation often leads to ineffective studies and a high risk of translational failure, as existing models fail to capture the complex clinical and biological features of human disease. One promising solution is the use of naturally occurring tumors in dogs. Hemangiosarcoma (hereafter referred to as angiosarcoma), a histologically similar counterpart to human angiosarcoma, occurs more frequently in domestic dogs. Canine angiosarcoma closely mirrors the clinical presentation and pathological characteristics of the human disease, offering a rich and translationally relevant research resource. Our previous work has demonstrated the experimental feasibility and technical advancements made possible by leveraging canine models for a variety of preclinical research applications. The use of animal models is justified as mouse xenograft systems derived from human and canine angiosarcoma tissues provide a controlled in vivo platform to evaluate tumor growth, RAS signaling, and therapeutic response in a pathologically relevant context that cannot be adequately modeled in vitro. The primary objective of this project is to establish a reliable translational model using canine angiosarcomas, with a particularly focus on cross-species molecular convergence into RAS signaling pathways. This pathway represents a promising therapeutic target for intervention using a tri-complex RAS(ON) multi-selective inhibitor. Specifically, we aim to: 1) establish multi-platform research resources from naturally occurring angiosarcoma in dogs; 2) assess the potential of canine angiosarcomas as a model for targeting active RAS signaling as a point of molecular convergence; and 3) develop AI models to assess the molecular relevance and translational potential of canine angiosarcoma. At the completion of the proposed project, we expect to generate comprehensive research resources to establish a reliable translational model for human angiosarcoma using naturally occurring cancers in dogs. This resource will enable us to demonstrate the therapeutic potential of the RAS(ON) inhibitor by effectively targeting convergent signaling pathways in angiosarcomas. AI models developed from canine angiosarcomas will support the clinical assessment of RAS-activated angiosarcomas by integrating complex genomic, molecular, and pathogenic characteristics. Through this approach, this project will offer strong translational applications for angiosarcoma, a rare and aggressive human vascular cancer. Furthermore, this project has the potential to establish a foundational modeling pipeline that can be adapted to support the use of naturally occurring cancers in dogs for translational research across a broad range of cancer types. Project Number: 1R01CA310992-01 | Fiscal Year: 2026 | NIH Institute/Center: National Cancer Institute (NCI) | Principal Investigator: Jong Hyuk Kim | Institution: UNIVERSITY OF FLORIDA, GAINESVILLE, FL | Award Amount: $635,324 | Activity Code: R01 | Study Section: Special Emphasis Panel[ZRG1 CTH-P (55)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11343984