Melanoma Program Project Summary / Abstract The Melanoma Program seeks to study all aspects of melanoma with the goal of advancing our understanding of the disease and translating the knowledge into improvements in diagnosis, prevention, and therapy to improve or save the lives of melanoma patients. Its members include international leaders who have made seminal contributions to both the basic understanding of melanoma and the management of patients, with direct impact on vastly improved clinical outcomes. Our collaborative research is embodied in part in a patient biopsy program coordinated by surgical and medical oncologists and dermatopathologists. Well- annotated tumor samples before, during, and after therapy enable deep understanding of genomic and molecular evolution in melanoma and address questions related to treatment responsiveness; this tumor bank is widely shared with investigators within and well beyond the Cancer Center. Beyond this resource, the Program has deep roots in basic research, translation, pivotal clinical trials, and in training outstanding melanoma researchers. The Program’s 43 members (35 primary and 8 secondary) represent all seven DF/HCC institutions and 10 academic departments. In 2019, peer-reviewed grant funding attributed to the Program was $2.4 million in direct costs from the NCI and $2.0 million from other sponsors. During the current funding period, primary Program members published 564 cancer-relevant papers. Of these 26% were inter-institutional, 18% were intra-programmatic, and 45% were inter-programmatic collaborations between two or more DF/HCC members. These numbers reflect the Program’s deeply interactive and collaborative ethos. To achieve the Program mission, our Specific Aims during the next CCSG funding period are to 1) Examine the molecular underpinnings of melanoma, comprised of genomics, epigenomics, and metabolomics, with the goal of leveraging the discoveries to optimize therapies for patients; 2) Investigate microenvironment features that modulate melanoma treatment responses; and 3) Study external factors that influence carcinogenic risk, behaviors relevant to melanoma-genesis, and treatment accessibility. To realize these Aims, Program members will take advantage of CCSG collaborative, clinical trial, and educational/training structures and exceptional core facilities.