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Start of funding 01.01.2008
Gene profiling of melanoma cells responsive to treatment with the multikinase inhibitor sorafenib (NexavarR)
Prof. Dr. Eckhart Kämpgen
Friedrich-Alexander-University of Erlangen-Nuremberg
Hautklinik - Universitätsklinikum Erlangen
Prof. Dr. Boris Bastian
University of California, San Francisco
Comprehensive Cancer Center
Better treatments of metastasized melanoma, the worldwide No1. malignancy causing death in young people < 30y, is a major challenge in oncology. Small-molecule drugs affecting essential molecular cell signal pathways have shown promising responses in various malignancies. At the Erlangen Dep. of Dermatology patients with documented progressive stage IV cutaneous or uveal melanoma emanating from EORTC trials 18032 (DTIC vs Temodal) and 18021 (Fotemustin) received additional treatment with the multikinase inhibitor Sorafenib showing partial responses and long term stabilization of the disease in 15 of 24 patients. Tumor cell lines from responder and non-responder patients and especially escape variants provide an ideal situation to characterize crucial molecular targets and mutations that confer resistance. The molecular analysis of signaling pathways and gene profiling will be undertaken as a joint project between the Erlangen Dep. of Dermatology (Prof. E. Kämpgen) and the University of California Comprehensive Cancer Center (Prof. B. Bastian). Results of the project are anticipated to have a major impact on future treatment of metastasized melanoma. First, identified gene polymorphisms will allow patient selection for treatment with Sorafenib and hopefully prolong patient survival. Second, identified mutations in escape variants should allow future design of kinase inhibitors with improved efficacy, higher specificity and broader applicability.