Tsipi Meshel

BEC brain endothelial cells BMMC brain-metastasizing melanoma cells BRD4 bromodomain containing 4 BRIRi brd4 and irs2 inhibitors CCL Chemokine (C-C motif) ligand DEG differentially expressed genes FACS fluorescence-activated cell sorting FCS fetal calf serum GAB2 grb2 associated binding protein 2 GAPDH glyceraldehyde 3-phosphate dehydrogenase HBB beta subunit of hemoglobin HSP70 Heat Shock Protein 70 IRS2 insulin receptor substrate 2 PARP poly (adp-ribose) polymerase PD-L1 programmed...

1. Introduction Melanoma incidence is rising yearly worldwide. Alongside the advance in new treatment options, brain metastases frequently develop in melanoma patients. Melanoma has one of the highest propensities to metastasize to the brain compared to other cancers, with 40–60% of melanoma patients developing brain metastases. At post-mortem dissections, central nervous system (CNS) involvement is identified in up to 80% of patients with metastatic melanoma.

1. Introduction Immunotherapies, whose aim is to potentiate anti-tumor immune activities, are now being implemented in the treatment of melanoma and of tumors with high mutation rates and DNA mismatch repair defects [1,2,3]. In breast cancer, immune checkpoint blockades (ICBs) have been introduced to the treatment of triple-negative breast cancers (TNBCs) that demonstrate relatively high genomic instability [4,5].