Pathobiology of Hemangiosarcoma in Dogs: Research Advances and Future Perspectives

Abstract

Hemangiosarcoma (HSA) is an aggressive and common cancer in dogs. While cutaneous masses are often treatable by tumor excision, visceral tumors are almost always incurable. Treatment advances for this disease have been limited due to a poor understanding of the overall tumor biology. Based upon its histological appearance, HSA has been presumed to originate from transformed endothelial cells; however, accumulating data now suggest a pluripotent bone marrow progenitor as the cell of origin for this disease. More recently, the identification of a novel subclassification of HSAs has provided a foundation to further our understanding of the cellular characteristics of HSA tumor cells, along with those of the cells comprising the tumor microenvironment. These discoveries hold promise for the development of new approaches to improve treatments for canine HSA, as well as to establish the utility of this disease as a spontaneous model to understand the pathogenesis and develop new treatments for vascular tumors of humans. In this review, we will provide a brief historical perspective and pathobiology of canine HSA, along with a focus on the recent advances in the molecular and cellular understanding of these tumors. In addition, future directions that should continue to improve our understanding of HSA pathogenesis will be discussed.

Retrospective comparison of first‐line adjuvant anthracycline vs metronomic‐based chemotherapy protocols in the treatment of stage I and II canine splenic haemangiosarcoma

“…Canine haemangiosarcoma (HSA) is an aggressive neoplasm that may arise in different anatomical locations including subcutaneous, intramuscular or visceral sites; the most common manifestation is the one affecting primarily the spleen . Treatment includes a combination of surgery and adjuvant chemotherapy.…”

Safe and Effective Sarcoma Therapy through Bispecific Targeting of EGFR and uPAR

“…Canine HSA is a common, aggressive, incurable spontaneous sarcoma that appears to have a similar ontogenetic origin as human angiosarcoma [9, 10–12]. Canine hemangiosarcoma and human angiosarcoma are both vasoformative sarcomas with similar microscopic appearance [13] that have often metastasized by the time they are diagnosed.…”

Emerging therapeutic approaches for canine sarcomas: Pushing the boundaries beyond the conventional

“…When considering vascular tumours, angiosarcoma in humans is a subset of soft tissue sarcomas that accounts for approximately 1% to 2% of all soft tissue sarcomas (~300 patients each year) and carries an overall poor prognosis with a high metastatic rate . With a similar, aggressive biologic behaviour to angiosarcoma, the incidence of canine hemangiosarcoma is estimated to be 25 to 100 times greater; but as with soft tissue sarcomas, the true incidence is unknown. Although human angiosarcoma and canine hemangiosarcoma are often viewed as homologous tumours, it is important to recognize that in humans, angiosarcoma includes tumours that arise from vascular endothelial cells (hemangiosarcoma) or lymphatic endothelial cells (lymphangiosarcoma) .…”

“…Although human angiosarcoma and canine hemangiosarcoma are often viewed as homologous tumours, it is important to recognize that in humans, angiosarcoma includes tumours that arise from vascular endothelial cells (hemangiosarcoma) or lymphatic endothelial cells (lymphangiosarcoma) . In dogs, these two distinct entities are still referred to separately with hemangiosarcoma predominating in the literature while lymphangiosarcomas are rare . For the purpose of this review, angiosarcoma refers to human hemangiosarcoma and lymphangiosarcoma while hemangiosarcoma refers to the canine vascular sarcoma, in keeping with current and historical literature.…”