SU2C Scientific Research Teams
SU2C-MRA Dream Team: Personalized Medicine for Patients with BRAF Wild-Type (BRAFwt) Cancer
Jeffrey M. Trent, Ph.D., F.A.C.M.G.
President and Research Director, Translational Genomics Research Institute (TGen)
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Patricia M. LoRusso, D.O.
Professor of Medicine and Associate Director of Innovative Medicine, Yale Cancer Center
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“Melanoma has been a success story in the past year, but that success affects about half of the patients, at best. We just said, we’ve got to go after that group that just desperately needs our help.” - Jeffrey M. Trent, Ph.D., F.A.C.M.G.
Each hour of each day in the United States, one person dies from metastatic melanoma, the most serious of all skin cancers. Metastatic melanoma refers to a cancer that has spread from the skin to other parts of the body, most frequently the lungs, muscle and liver. Nearly half of all patients with metastatic melanoma have an alteration in a particular gene called BRAF. For these patients, recent efforts of cancer researchers have resulted in promising treatment options that directly target the specific BRAF alteration. However, for those metastatic melanoma patients who have no such BRAF alteration, few effective treatments and no cures exist. For this group of patients in particular, it is vital that new targets for therapy be found.
Recent advances in our knowledge of human genetics have enabled us to consider new approaches to how we treat cancer. One such approach involves the study of a person’s “genome,” which is the entire set of genetic instructions found in a cell – an amazing 3.1 billion bases of DNA sequence. The ability to examine the changes in the genome of a patient with cancer has never been greater than it is today, both in terms of speed and cost. This is due in large part to the maturation of so-called next-generation sequencing technology, which allows the DNA of the entire genome to be sequenced far less expensively and with far greater accuracy than ever before.
The goal of the SU2C-MRA Melanoma Dream Team Translational Cancer Research Grant led by Jeffrey M. Trent, Ph.D., and Patricia M. LoRusso, D.O., is to use next-generation sequencing technology to examine both the normal and cancer genome of patients with metastatic melanoma. Patients whose melanoma tumors do not have BRAF alterations will have other specific genetic alterations identified and these changes will be matched to an appropriate therapy that directly targets those alterations. The hope is that this “personalized medicine” approach will lead to more effective and lasting treatments and potentially spare patients from unnecessary treatments that are expensive, highly toxic and all too often provide little or no benefit.
Trent and LoRusso have assembled a Dream Team of colleagues with outstanding clinical, genomic, computer science and drug development expertise – all intent on matching the underlying genetic causes with individualized treatment plans for patients with metastatic melanoma. Through their combined efforts, they propose to refine and standardize the process for matching the right treatment with the right patient, based on each person’s genetic makeup. Armed with this knowledge, and the results of an initial feasibility study, the Dream Team will conduct a clinical trial to evaluate if personalized therapy, based on the genetic profile of each individual patient’s cancer, improves outcomes. If successful, this precision medicine approach may not only benefit metastatic melanoma patients, but could also serve as a model for other types of cancers.
Watch a short video in which the SU2C-MRA Melanoma Dream Team leaders Trent and LoRusso talk about the science behind their project: