Angiosarcoma (AS) is a highly aggressive tumor of blood and lymphatic vessels in humans that carries a poor prognosis. The rarity of AS, together with its heterogeneous nature, and locations (skin, breast, visceral organs and deep soft tissues), makes understanding the pathogenesis of AS challenging. Dogs and cats spontaneously develop hemangiosarcoma (HSA), an aggressive tumor that shares many histopathological and clinical similarities to AS. To investigate the genetic suitability of spontaneously occurring HSA as a model for AS, we sequenced ∼1,000 cancer genes in 41 cases of HSA and matched germline tissue; 15 canine visceral HSAs, 13 canine skin HSAs and 13 feline skin HSAs. Analysis of visceral HSAs from dogs presenting with concurrent splenic and cardiac neoplasms showed that the tumors were not independent primaries, consistent with the highly metastatic nature of HSA. Comparison of canine and feline HSA to human AS revealed that several driver genes were recurrently mutated in both species, such as TP53, PIK3CA, ATRX, GRIN2A and LRP1B. In the germlines, by focusing specifically on canine and feline orthologs of human AS risk genes, we identified several candidate pathogenic variants. Similar to AS, a UV mutational signature was found in a subset of canine cutaneous HSAs. Furthermore, both AS and canine HSA show differing mutational profiles between tissue sites. Our characterization of canine and feline HSA demonstrate many important parallels to AS and provides hope that future studies on these cancers will benefit patients of all three species.

Dogs diagnosed with appendicular osteosarcoma typically succumb to metastatic disease within a year of diagnosis. The current standard of care for curative intent, amputation followed by adjuvant chemotherapy, increases survival time but chemoresistance is a major contributor to mortality. Unfortunately, the mechanisms driving the progression of metastatic disease and the development of chemoresistance are unknown. One theory is that autophagy may contribute to chemoresistance by providing neoplastic cells with a mechanism to survive chemotherapy treatment. Our objective was to evaluate the effect of combining an autophagy inhibitor with a standard chemotherapeutic drug on response to chemotherapy in canine appendicular osteosarcoma cells. We hypothesized that combining the autophagy inhibitor spautin-1 with doxorubicin treatment would enhance chemoresponsiveness. Using commercial (D17) and primary cell lines derived from 1° and 2° sites of osteosarcoma, we showed that this combination treatment enhances cell killing and inhibits colony formation. Our findings support the theory that autophagy contributes to chemoresistance in canine appendicular osteosarcoma and indicate that adding an autophagy inhibitor to the standard of care has the potential to improve outcome.

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Cancer is a significant cause of morbidity and mortality in domestic cats. In humans, an understanding of the oncogenome of different cancer types has proven critical and is deeply interwoven into all aspects of patient care, including diagnostics, prognostics and treatments through the application of targeted therapies. Investigations into understanding the genetics of feline cancers started with cytogenetics and was then expanded to studies at a gene-specific level, looking for mutations and expression level changes of genes that are commonly mutated in human cancers. Methylation studies have also been performed and together with a recently generated high-quality reference genome for cats, next-generation sequencing studies are starting to deliver results. This review summarises what is currently known of the genetics of both common and rare cancer types in cats, including lymphomas, mammary tumours, squamous cell carcinomas, soft tissue tumours, mast cell tumours, haemangiosarcomas, pulmonary carcinomas, pancreatic carcinomas and osteosarcomas. Shining a spotlight on our current understanding of the feline oncogenome will hopefully serve as a springboard for more much-needed research into the genetics of cancer in domestic cats.

A 6.2-year-old 28-kg (61.7 lb) intact female Golden Retriever was referred due to persistent and multiple cytopenias noted on a routine CBC prior to a mature ovariohysterectomy procedure. The patient's physical examination was unremarkable, and staging of the thorax and abdomen identified no abnormalities. At the referral hospital, moderate hypercalcemia, borderline anemia, and neutropenia were noted.