Immunomodulatory aspects of drug resistance in melanoma target therapy

Incidence of cutaneous melanoma (CM) has continued to rise in recent years due to aging population and UV exposure. CM displays high genetic variability; one of the most common mutations is BRAF-V600E, found in 40-60% of cases, which causes continuous activation of the MAPK/ERK pathway resulting in uncontrolled cell growth. One of the first-line treatments in CM is the combinational therapy of BRAF inhibitors with MEK inhibitors, that substantially reduces tumor burden. A major challenge is melanoma’s ability to become more aggressive and develop resistance after a few months of starting therapy, forcing doctors to modify their treatment strategies. This study aims to examine differences in the expression of various immune markers between naïve and drug-resistant (DR) cells. Specifically, it focuses on CD24, IL-6 and CCL2, which are upregulated in DR cells across several models in humans and mice. We aim to investigate the immune system’s role in targeted therapy resistance using in vivo and in vitro models. The involvement of these markers in CM resistance to targeted therapy could lead to identifying new therapeutic targets and advancing new treatments.