Melanoma is a cancer of melanocytes, the cells responsible for pigment production in the body. While melanoma has one of the highest cure rates of any cancer when detected early, once melanoma has metastasized the chances of survival dramatically decrease. Fortunately, the approval of numerous targeted and immune-based therapies for metastatic melanoma have had a significant impact on patient survival in the past 8 years. An important catalyst of this therapeutic success has been our significant understanding of the biology and genetics of melanoma. Genomic platforms, including next-generation sequencing, have rapidly increased our knowledge into the diverse sub-types of melanoma. This has allowed us to extract meaningful diagnostic information for use in the clinical management of patients, given us insight into the potential causes of melanoma, and have helped us identify new drug targets. Despite this, drug-resistance, patients not responding to treatment, and unintended side effects are all issues that need to be resolved by the field. In this talk, I will provide an overview of the somatic genetics of melanoma and discuss its diagnostic relevance in context to the current landscape of therapies for late-stage disease. This will be followed by my recent research on understanding the role and potential mechanisms of transcriptional cell states in melanoma and its significance in up-front and acquired drug resistance. Lastly, I will provide an overview of my collaborative efforts with the Broad Institute of Harvard MIT to identify melanoma specific gene dependencies as novel drug targets through use of genome-wide CRISPRknockout screens.
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