A Comparative View on Molecular Alterations and Potential Therapeutic Strategies for Canine Oral Melanoma

Abstract

Canine oral melanoma (COM) is a highly aggressive tumour associated with poor prognosis due to metastasis and resistance to conventional anti-cancer therapies. As with human mucosal melanoma, the mutational landscape is predominated by copy number aberrations and chromosomal structural variants, but differences in study cohorts and/or tumour heterogeneity can lead to discordant results regarding the nature of specific genes affected. This review discusses somatic molecular alterations in COM that result from single nucleotide variations, copy number changes, chromosomal rearrangements, and/or dysregulation of small non-coding RNAs. A cross-species comparison highlights notable recurrent aberrations, and functionally grouping dysregulated proteins reveals unifying biological pathways that may be critical for oncogenesis and metastasis. Finally, potential therapeutic strategies are considered to target these pathways in canine patients, and the benefits of collaboration between science, medical, and veterinary communities are emphasised.

The human and animals’ malignant melanoma: comparative tumor models and the role of microbiome in dogs and humans

“…However, some dog breeds are more affected, which suggests a genetic basis [1,65]. Even so, there is not total unanimity on which breeds are the most susceptible [68]; some researchers report an increased predisposition for Golden Retrievers, Cocker Spaniels, Miniature Poodles, Chow Chows, Gordon Setters, and Anatolian Sheep Dogs [56,69,70], while others do not find an overall breed predisposition [71]. Usually, affected dogs have very pigmented oral mucosa and skin; however, predisposing germline alleles have not been determined [51,72].…”

Tumor-Associated Macrophages in Canine Oral and Cutaneous Melanomas and Melanocytomas: Phenotypic and Prognostic Assessment

“…Studying TAMs both as prognostic indicators and as therapeutic targets in canine melanocytic tumors seems to be a promising path to follow to increase the current knowledge of their role in these tumors. Indeed, melanocytic tumors, despite being common in dogs, have sometimes unpredictable behavior and no curative available therapies (23)(24)(25)(26)(27); therefore, studies investigating additional valid prognostic features and feasible targets for new therapeutic strategies are fundamental.…”

Advances in Understanding Spontaneously Occurring Melanoma in Animals

“…A critical review of the treatment options available for canine oral melanomas by Pazzi and colleagues evaluates the current literature on this topic and provides treatment recommendations and suggestions for future canine oral melanoma research [ 8 ]. Hardwick reviews the somatic molecular alterations that are seen in canine oral melanomas, from single nucleotide variations to chromosomal rearrangements and dysregulation of snRNAs, and performs a cross-species comparison with human mucosal melanoma to identify recurrent aberrations and reveal biological pathways that may be critical for tumourigenesis and metastasis, with a view to considering these as potential therapeutic targets [ 9 ]. Oncept is xenogeneic DNA vaccine targeting human tyrosinase that has been USDA-approved since 2007 for the treatment of canine oral melanoma (stage II-III), as well as being used off-label for melanomas arising in other locations and species.…”