Congenital melanocytic nevi (CMN) are benign melanocytic neoplasms that vary in genetic drivers leading to the formation of pigmented lesions. Activation of Mitogen-Activated Protein Kinase (MAPK) pathway members through oncogenic mutations of NRAS or BRAF and more rarely by gene fusions allow expansion of nevomelanocytes to form CMN. Pre-clinical approaches to CMN therapy are expanding with the use of small-molecular inhibitors to mitogen-activated protein kinase kinase (MEK), RNA-based therapeutic approaches, and leveraging topical immunotherapy to regress nevi using in vitro and in vivo models and select case reports. Continued identification of CMN drivers combined with emerging therapeutic strategies will help improve CMN patient response and outcomes in the future.

Congenital Melanocytic Nevi (CMN), NRAS, BRAF, Mitogen-activated Protein Kinase (MAPK) pathway, MAPK Targeted Therapy, RNA-based Therapy, Topical immunotherapy, Trametinib, Binimetinib, SADBE