Personalized Medicine for Patients with BRAF wild-type (BRAFwt) Cancer

About half of the patients with metastatic melanoma (MM) have a mutation in the BRAF gene. While recently developed inhibitors have demonstrated clinical efficacy in these patients, little progress has been made in identifying therapeutic targets to treat the other half ?those patients with wild-type BRAF (BRAFwt) tumors. This latter cohort is likely to reap the benefit of genome-based treatments (i.e., personalized medicine). The goal of the Dream Team led by Drs. Trent and LoRusso is to select patients for sensitive mutations and match them to appropriate therapies based on their individual genomic signature. The hope is that such an approach may lead to more effective and durable therapeutic interventions over an unselective standard approach, potentially sparing patients from unnecessary toxicity, expense, and time wasted on ineffective therapies; time patients do not have. Drs. Trent and LoRusso have assembled a Dream Team of colleagues with expertise in the medical management of patients with MM, drug development, genomics research, biostatistics, and bioinformatics. They propose to iteratively refine and standardize statistical and informatics methodologies for matching treatments to the patients tumor, based on their individual molecular profile. Armed with this knowledge, and the results of an initial feasibility study, they will conduct a randomized clinical trial to evaluate if molecularly-informed personalized therapy selection, based on a patients tumor molecular profile, improves outcomes when compared to standard of care therapy in BRAFwt MM. If successful, this individualized medicine approach to the treatment of BRAFwt MM will not only lead to therapeutic benefit for this patient population, but may also serve as a new paradigm for many other tumor and disease types.