Animal Models of Melanoma

The worldwide incidence of malignant melanoma is rising faster than any other cancer, and in the United States alone, almost 50,000 new cases of melanoma were projected for the year 2000. While thin primary melanomas are highly curable with surgery, the prognosis for patients with advanced disease is poor: Over 70% of patients with primary melanomas thicker than 4 mm or metastasis to the regional lymph nodes will die of disseminated disease within 5 yr of diagnosis. The treatment of metastatic disease has undergone significant changes over the past two decades with the introduction of high-dose cytokine therapy (e.g., interferon-alpha and interleukin-2), biochemotherapeutic regimens, novel vaccination strategies, and sentinel lymph-node biopsy techniques. Despite these advances, and a better understanding of the molecular lesions underlying the development of the malignant phenotype, the therapeutic options for patients with metastatic disease remain limited. High-dose cytokine therapy infrequently produces durable responses and is often poorly tolerated by patients with advanced disease. Aggressive chemotherapeutic regimens have not consistently proved superior to therapy with single agents, and the improved response rates achievable with biochemotherapy come at the price of significant toxicity. Other approaches to the patient with advanced disease, such as peptide and anti-ganglioside vaccines, remain investigational. Thus, it is critical that novel regimens with favorable toxicity profiles enter into clinical development. In order to move new treatments rapidly into the clinic and to gain a better understanding of their mechanism of action, it is essential that experiments be conducted in animal models of malignant melanoma. This chapter reviews those models that are currently in use and explores their strengths and disadvantages.