Treatment of canine haemangiosarcoma with suberoylanilide hydroxamic acid, a histone deacetylase inhibitor

A case report is presented by describing the treatment of a 12-year-old dog - diagnosed with haemangiosarcoma (HSA) - with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor. The drug was administered orally, on a daily basis, approximately 2 weeks post-splenectomy at a dose of 3 mg kg(-1). HSA is a lethal malignancy of the endothelium, which is usually disseminated by the time it is diagnosed. Median survival time, usually, is no longer than 80 days. Following treatment with SAHA, no sign of malignant growth could be discerned by means of diagnostic abdominal ultrasound, chest X-ray or with the help of clinical symptoms, over a period of >1000 days. The precise mechanism by which HDAC inhibitors exert their anti-cancer effects is uncertain, but evidence suggests that exposure to SAHA generates hyperacetylated chromosomal histones, which, in turn, facilitates the expression of tumour suppressor genes turned off by epigenetic mechanisms during neoplastic transformation of the endothelium.