ACRAL LENTIGINOUS MELANOMA IN MOLECULAR ANALYSIS AND THERAPY

Abstract

Acral lentiginous melanoma (ALM) represents a rare and distinct subtype of cutaneous melanoma, characterized by a low association with ultraviolet radiation and a unique molecular profile. The predominance of this subtype in the glabrous palmoplantar skin and nail bed, as well as its prevalent incidence in people of African descent, Asians, and Hispanics, increase its specificity. From this perspective, this study aimed to review the main genetic alterations and their molecular peculiarities, as well as the signaling pathways involved in tumorigenesis and their therapeutic implications. To this end, the study conducted an integrative literature review by analyzing articles published between 2019 and 2025, indexed in the PubMed, SciELO, and CAPES Periodicals databases. The review included randomized clinical trials and meta-analyses, peer-reviewed, and articles that contained methodological bias, were unavailable in full text, or deviated from the topic were excluded. The results show a predominance of structural chromosomal alterations, with emphasis on amplifications in KIT, CCND1, CDK4, and TERT, finding that mutations in NF1, BRAF, and NRAS are less frequent when compared to other subtypes of melanoma in photoexposed areas. The MAPK and PI3K/AKT pathways were central to tumor progression, as were chromosomal rearrangements in 11q13 and 5p15, commonly associated with genomic disorganization. Therefore, it can be concluded that the molecular profile of MLA supports a unique genetic landscape, which should guide diagnostic and therapeutic methods. This heterogeneity reinforces the need for individualized strategies, aiming to reduce late diagnosis, which limits prognosis, and advance targeted therapies.