Investigating the effects of venom peptides on canine mammary cancer

Mammary Cancer is the most prevalent form of malignancy to occur in female dogs. With metastasised malignancies representing 50% of diagnosis, current treatments produce little efficacy towards survival and induce harsh adverse side effects, thus there is need for novel therapeutics. Venoms have been shown to exploit anti-cancer properties with specific selective effects towards many forms of human cancers, thus, the prospect of anti-cancer inhibition towards Canine Mammary Cancer is a feasible hypothesis. Utilising in-vitro cell viability assays, panels of venoms from snake, scorpions and spiders were profiled against canine mammary cancer cells lines, CMT28 and CMM26, and an immortalised normal canine kidney cell line, MDCK. Screening of these venom fractions identified selectivity towards the cancerous cells utilising venoms from the Naja genus by >70% inhibition. Mass spectrometry data of 5 fractions identified them as 3-finger toxins with 3 of the fractions identifying as novel cytotoxins and 2 matched to sequence in the database of the same species. Epidermal Growth factor receptor- 2 (HER2) is a key antigenic target in Human breast cancer and has been shown to be as a potential therapeutic target for Canine Mammary Cancer. Utilising computational modelling and molecular docking simulations, the identified cytotoxins obtained from mass spectrometry have been predicted to bind to the dimerisation loop of the extracellular domain of HER2, that is hypothesised to inhibit dimer formation. In practice Canine HER2 demonstrated to have a high binding affinity for proteins in whole snake venoms, signifying the potential of HER2 being a therapeutic target for the treatment of Canine Mammary Cancer