Molecular Profile of Canine Hemangiosarcoma and Potential Novel Therapeutic Targets

Abstract

Canine hemangiosarcoma (HSA) is a relatively common neoplasia, occurring mainly in the skin, spleen, liver and right atrium. Despite the numerous studies investigating the treatment of canine HSA, no significant improvement in survival has been achieved in the last 20 years. Advancements in genetic and molecular profiling presented molecular similarities between canine HSA and human angiosarcoma. It could therefore serve as a valuable model for investigating new and more effective treatments in people and dogs. The most common genetic abnormalities in canine HSA have been found in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and neuroblastoma RAS viral oncogene homolog (NRAS) pathways. Mutations are also found in tumor protein p53 (TP53), phosphatase and tensin homolog (PTEN) and cyclin dependent kinase inhibitor 2A (CDKN2A). Known abnormal protein expression could be exploited to trial new target treatments that could be beneficial for both canine and human patients. Despite the high expression of vascular endothelial growth factor (VEGF) and its receptor (VEGFR), no correlation with overall survival time has ever been found. In this review, we explore the most recent developments in molecular profiling in canine HSA and discuss their possible applications in the prognosis and treatment of this fatal disease.

Tumor Immune Microenvironment and Its Clinicopathological and Prognostic Associations in Canine Splenic Hemangiosarcoma

“…Hemangiosarcoma (HSA) is a malignant tumor of dogs presenting in various anatomical forms with distinct biologic behaviors, based on their cell of origin. Recent studies suggest that cutaneous hemangiosarcoma likely originates from transformed mature endothelial origin, exhibiting a comparatively better biologic behavior with rare metastases, whereas other forms of HSA likely arise from the precursor (pluripotent) endothelial cell in the bone marrow, subsequently migrating and colonizing organs with viable microenvironments (spleen, liver, right atrium) [1][2][3]. In the spleen, HSA is the most common neoplasm, representing 50-74% of all splenic malignancies in dogs [4,5].…”

“…The survival time usually ranges between 19 days and 260 days [6]. Recent comparative genomic studies have revealed a shared genomic landscape between canine HSA and human angiosarcoma of the breast and viscera, suggesting that the dog can be considered a useful model for the study of human angiosarcoma [3,[7][8][9][10][11][12][13][14].…”