Researchers in the Melanoma Research Program are involved in a wide variety of research projects.
Duke is home to the largest regional chemotherapy program in the United States for patients with advanced extremity melanoma. Duke surgeons are among the national leaders in developing novel techniques and treatment strategies that allow regional delivery of new therapeutic agents to an extremity affected by melanoma. These regional treatments allow high doses of chemotherapy to be given without affecting the rest of the patient’s body.
Advancing vaccine therapy. With a long history of pioneering vaccine development in melanoma, Duke is working to develop a new generation of tumor vaccines. The new vaccines are designed to augment the function of the body’s main immune-fighting cell, the dendritic cell. A phase 1 study, open to subjects with metastatic melanoma, is assessing vaccination with melanoma tumor-associated antigen-encoding RNA-transfected mature dendritic cells. Duke also employs state of the art immunologic monitoring techniques to determine if various treatment be they vaccines or regional therapies help augment anti-tumor immunologic responses.
One of the world’s largest melanoma databases. Duke has prospectively maintained a database of melanoma patients for over three decades -- the largest melanoma registry in the world. The database contains over 14,000 patients. This resource is managed by a multidisciplinary board and enables researchers to perform retrospective analyses of recurrence patterns and other outcomes.
Laser evaluation technology. Duke is one of only a handful of centers using a reflectance confocal microscope to diagnose and study melanoma. The laser microscope lets clinicians and researchers look into the skin to a depth of about 0.4 mm with near histologic-level resolution, to help determine if an area is skin cancer without a biopsy. The tool also allows one to see the blood moving through blood vessels and to study vascular morphology in tumors in real-time. There are approximately 30 confocal microscopes in use in the world.
Basic / Translational Research
Areas of significant focus in the basic sciences include cell signaling where research is being carried out looking at critical proteins in melanoma growth such as Braf and glutathione-s-transferase. The laboratory of Chris Counter, PhD, studies how copper metabolism can be targeted to stop growth signals generated by mutations in the Braf protein that are common in melanoma. The laboratory of Francis Ali-Osman, DSc, studies the effects of the protein glutathione-s-transferase as a major regulator of MAP kinase signaling, much like the Braf protein, in melanoma and how targeting this proteins can arrest melanoma growth.
Many laboratories also focus on immunologic ways to overcome melanoma growth including vaccine development in the laboratories of Scott Pruitt, MD, PhD, and Smita Nair, PhD, immunologic monitoring of patients with melanoma in the laboratories of Kent Weinhold, PhD, and Cliburn Chan, PhD, and how cell signaling focused on the protein TGFbeta in the laboratory of Gerry Blobe, MD, PhD can modulate the immune system and effect the growth of melanoma tumors. These groups have translated their work in to novel dendritic cell vaccine trials currently open at Duke which are run by Pruitt.
Overcoming melanoma chemoresistance is another focus of Duke researchers especially for tumor recurrence called in–transit disease as well as metastatic disease. The laboratories of Douglas Tyler, MD, Paul Mosca, MD, PhD, and Mark Dewhirst, DVM, PhD, have developed several novel targeted approaches to make chemotherapy work better in patients and have several clinical trials currently open based upon work that has come out of their combined efforts. This group has work closely with the laboratory of Joseph Nevins, PhD, and Christi Augustine, PhD, to develop unique ways of reading genes obtained from analysis of biopsies from patient tumors. These studies have helped to derive personalized approaches to patient care for certain subsets of melanoma patients.
Finally developing optimal patient treatment algorthyms based upon analysis of our large melanoma database and quality of life measures has been the focus of the research program led by Amy Abernethy, MD, and involving April Salama, MD, and Randy Scheri, MD, which has the goal of optimizing as well as streamlining the care of patients with various stages of melanoma in light of new treatment options currently available.