Malignant Melanoma

  • Melanocytic lesions arising from the oral mucosa or cutaneous epithelium in the dog are common (<100,000 cases per year).

  • Canine cutaneous melanomas are often benign, however oral melanomas are highly aggressive and most dogs with stage II or III disease succumb to pulmonary metastatic disease within 3-12 months of diagnosis. ​

  • Similar molecular pathway aberrancies have been identified in canine and human malignant melanoma lesions including c-KIT mutations, AKT mTOR pathway activation, Wnt/B-catenin pathway dysregulation and increased COX2 expression. Copy number gain of the oncogene c-MYC and loss of CDKN2A are also common.

  • Unlike human cutaneous malignant melanoma, mutations in the B-RAF oncogene are uncommon in human mucosal melanoma and uncommon in canine oral malignant melanoma. 

  • Standard of care treatment of canine oral malignant melanoma involves loco-regional control using surgery or radiation. Adjunct chemotherapy is generally not effective at preventing or treating metastatic disease.

 

  • Immunotherapy for malignant melanoma in both species has shown promise. In human disease, checkpoint blockade using anti-CTLA4 and anti-PD-1 antibodies or Tumor Infiltrating Lymphocytes have produced dramatic responses in some cases. 

 

  • Clinical studies using adoptive cellular therapies combined with agonistic cytokines in dogs with oral malignant melanoma aim to accelerate this approach for human patients and investigation go correlative biomarkers of response in canine patients may help to inform human clinical trials. 

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