The Molecular Basis of Canine Melanoma: Pathogenesis and Trends in Diagnosis and Therapy

Abstract

Melanoma is a common neoplastic disease of dogs with variable presentation and biological behavior. Canine malignant melanoma is a rapidly metastatic disease that generally is incurable. The loss of function of cellular safeguards built into the genetic program and of immune surveillance systems that cooperate to prevent tumor formation and progression appear to be important underlying causes of canine malignant melanoma. In effect, many existing cancer treatments restore the function of 1 or the other of these mechanisms. For example, chemotherapy and radiotherapy often kill tumor cells by initiating a genetic suicide mechanism (apoptosis), and immunotherapy initiates or enhances a response by the body's immune cells to identify and destroy cancer cells by mechanisms that rely on direct cytotoxicity or apoptotic cell death. Nevertheless, standard therapeutic approaches have not proved effective in treatment of canine malignant melanoma, with only marginal improvement in the outcome of dogs with this disease. The advantages of an improved understanding of the molecular basis of canine cancer are underscored by recent promising advances in diagnosis and in immunologic and genetic therapies that may help reduce the mortality of dogs affected with malignant melanoma.

Malignant Melanoma of the Syrinx and Liver in an African Grey Parrot (Psittacus erithacus erithacus)

“…7 Several pathogeneses of melanoma have been described in dogs. 20 Exposure to ultraviolet radiation across all breeds and genetic factors in purebred dogs have been implicated in mutations that lead to melanoma. The underlying cause of neoplastic transformation in the African grey parrot we describe is unclear because both exposure to ultraviolet radiation and genetic predisposition are unlikely, based on the location of the tumors and the rarity of melanoma in avian species.…”

The Skin

“…43 Although our understanding of the pathogenesis of canine melanoma is incomplete, alterations in expression or function of genes and proteins involved in cell cycle control and cell death may be of importance in the development of melanomas. 49 Clinical Features. Melanomas occur in dogs and cats at an average age of 9 years.…”

Treatment Efficacy and Immune Stimulation by AdCD40L Gene Therapy of Spontaneous Canine Malignant Melanoma

“…2,4 Genetic and molecular factors that have been associated with canine malignant melanoma include p53, metallothionein, RB-1, PTEN, N-ras, cyclin kinase inhibitors, and some angiogenic factors. [7][8][9][10] It is interesting to note that the same factors are also involved in the pathogenesis of human melanomas, which supports the utility of comparative medicine, [9][10][11] and suggests that canine malignant melanoma is a good spontaneous clinical model for the development of new therapies for humans. [12][13][14][15][16] Malignant melanoma is primarily a disease of older dogs.…”

“…3,5 Most canine oropharyngeal, uveal, ungual, and mucocutaneous melanomas are aggressive, with severe local infiltration and a high metastatic potential to lymph nodes, lungs, liver, and kidneys. 3,6,7 The etiology of melanocytic tumors in dogs is largely unknown, but as the oral cavity and haired skin are the most common places for these tumors, an etiology involving ionizing sunlight is unlikely. Breed seems to influence both incidence and prognosis, suggesting the contribution of genetic factors.…”