| The current standard of care treatment for canine histiocytic sarcoma (HS) is based on the administration of conventional chemotherapeutic drugs, which results in low percentage of partial and short-term favorable responses. In order to identify novel drug candidates for the treatment of dogs with HS, we investigated the cytostatic activity of a panel of sixteen compounds over two canine HS cell lines. Our results demonstrated that dasatinib, a receptor tyrosine kinase pan-inhibitor, and other novel molecularly-targeted drugs JQ1, a BET bromodomain inhibitor, and bortezomib, a proteasome inhibitor, effectively inhibited the growth of HS cells in vitro. The antiproliferative response of dasatinib was augmented when combined to doxorubicin, a classical chemotherapeutic agent. For all these drugs, the effective inhibitory concentration in vitro was within a clinically achievable and tolerable plasma concentration in vivo, as described in the veterinary and human medicine literature. In this study we identified three molecularly targeted drugs that may represent a promising anticancer strategy for canine HS. Further in vivo studies and clinical trials are needed to fully evaluate therapeutic potential of these drugs in HS in dogs and in similar disorders in humans. |
