Towards minimal residual disease-directed therapy in melanoma. Towards minimal residual disease-directed therapy in melanoma

Many patients with advanced cancers achieve dramatic responses to a panoply of therapeutics, yet retain minimal residual disease (MRD), which ultimately results in relapse. To gain insights into the biology of MRD we applied single-cell RNA-sequencing to malignant cells isolated from BRAF-mutant patient-derived xenograft (PDX) melanoma cohorts exposed to concurrent RAF/MEK-inhibition. Overall design: We performed single cell RNA and single cell DNA sequencing from a PDX melanoma model before and on treatment (BRAF&MEK inhibitors). Furthermore, we performed bulk RNAseq of in vitro cultures that were derived from our PDX model, which were treated with BRAF and MEK inhibitors and FACS sorted for GFRA2high and low cells.