Center for Advanced Preclinical Research: Cutaneous Malignant Melanoma

Lung metastasis in HGF;CDK4 melanoma model
Lung metastasis in HGF;CDK4 melanoma model

de novo genetically engineered murine (GEM) models develop melanomas in response to UV radiation that are consistent with major molecular subtypes (e.g., BRAF mutation):

  • BRAFV600E-driven melanoma, based on the model described by Dankort et al. (Nature Genetics 41:544-52, 2009)
  • Wildtype BRAF/NRAS melanoma, based on the aberrant HGF-MET signaling model described by Noonan et al. (Nature 413:271-2, 2001) and Tormo et al. (Am. J. Path. 169:665-72, 2006)
  • HGF/CDKN2A tumors resemble human melanoma with respect to histopathology, molecular biology and etiology
  • Melanocytic lesions develop in stages from benign nevi to metastatic melanoma
  • Preclinical murine models of metastatic melanoma are created for therapeutic evaluation based on GEM-Derived Allografts (GDAs)
  • Preclinical studies are conducted using transplanted melanoma tissues that have never been adapted to cell culture
  • Studies are conducted in fully immunocompetent mice, permitting assessment of immunotherapeutic agents
  • Therapeutic trials are with an industry-friendly turnaround time of approximately 6-8 weeks
  • Tumor dynamics and drug responses are followed by bioluminescent imaging and biomarker assessment