Plasma proteome alterations by MAPK inhibitors in BRAFV600-mutated metastatic cutaneous melanoma☆☆☆
Highlights • Based on antibody-based proteomics by proximity extension assays, pre-treatment levels of several proteins were predictive of shorter progression-free survival (PFS) after treatment with MAPK-inhibitors in metastatic cutaneous melanoma (CM), including IL6, IL10, CCL-2/-3/-4, LGALS1, and CSF1.• By in-depth mass-spectrometry-based proteomic analysis of 1,160 proteins in a subset of metastatic CM patients receiving BRAF- and MEK- inhibitors, we discovered alterations in plasma proteins involved in cell adhesion-, neutrophil degranulation-, and proteolysis- during BRAFi and MEKi treatment.• CPB1 had the highest increase during BRAF- and MEK- inhibitors’ treatment and was associated with longer PFS.• Most of the proteins altered in plasma during MAPKi treatment were traceable to BRAFV600E-mutated metastatic CM tissue at mRNA level, based on expression patterns in 154 patients from the TCGA cohort.