Currently, patients who develop metastatic melanoma have a dismal prognosis, with a median survival of six to nine months and a three-year survival rate of 10 percent to 15 percent. About half of patients with metastatic melanoma have an oncogenic mutation in their tumor’s BRAF gene, but the other half of patients are BRAF wild type (BRAFwt) and have no mutation in the gene. Very little progress has been made to identify new therapeutic targets to treat metastatic melanoma patients with BRAFwt disease.
This project will investigate the utility of personalized target/therapy identification in patients with BRAFwt metastatic melanoma. The goal is a significant improvement in tumor response relative to standard-of-care therapy. This Dream Team hopes that an individualized medicine approach to the treatment of BRAFwt metastatic melanoma will not only lead to therapeutic benefit for this patient population, but may also be beneficial to many other tumor and disease types.
Specific Research Goals:
- Use next-generation sequencing technology to examine both the normal and cancer genome of patients with metastatic melanoma.
- Generate models that predict the sensitivity of BRAFwt melanomas to specific drugs by molecularly profiling BRAFwt and BRAF-mutant cell lines and testing for sensitivity to 100 prioritized compounds that might translate into therapeutic utility.
- Test these predictions by using xenografts of the melanoma cell lines as well as primary tumors.
- Determine whether this personalized approach significantly improves clinical outcome by conducting a clinical trial using the information gained from the previous goals.
Amount of Funding:
Jeffrey M. Trent, Ph.D., F.A.C.M.G., president and research director at The Translational Genomics Research Institute (TGEN) and the Van Andel Research Institute (VARI)
Patricia M. LoRusso, D.O., director, Center for Experimental Therapeutics, Karmanos Cancer Institute and Wayne State University School of Medicine
Joshua LaBaer, M.D., Ph.D., director, Virginia G. Piper Center for Personalized Diagnostics, Arizona State University Biodesign Institute
Brian J. Nickoloff, M.D., Ph.D., professor and division director, dermatology, Michigan State University
College of Human Medicine
Svetomir Markovic, M.D., Ph.D., professor of medicine and oncology, Division of Hematology, Mayo Clinic College of Medicine
Neal Rosen, M.D., Ph.D., member, Department of Medical and Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center
Aleksandar Sekulic, M.D., Ph.D., assistant professor, Department of Dermatology, Mayo Clinic Arizona
Nicholas J. Schork, Ph.D., director, Bioinformatics and Biostatistics, Scripps Research Institute
Jeffrey A. Sosman, M.D., professor of medicine, Vanderbilt University Medical Center
Kristiina Vuori, M.D., PhD., president, professor and Pauline and Stanley Foster presidential chair
Sanford-Burnham Medical Research Institute
Craig P. Webb, Ph.D., principal investigator, Van Andel Research Institute
Connie Mack III
Page updated: June 6, 2012