Lipidomics in Melanoma: Insights into Disease Progression and Therapeutical Targets

TL;DR

This paper explores how changes in lipid metabolism contribute to melanoma progression and resistance to treatment, suggesting new therapeutic strategies.

Contribution

The paper provides a comprehensive review of lipid metabolic reprogramming in melanoma and its implications for therapy.

Findings

Lipid metabolic reprogramming supports melanoma cell survival and resistance to therapies.

Advances in lipidomics technologies enable detailed profiling of lipid alterations in melanoma.

Targeting lipid metabolic pathways offers potential for improved melanoma diagnosis and treatment.

Abstract

Melanoma is the deadliest form of skin cancer, characterized by high metastatic potential and intrinsic heterogeneity. In addition to genetic mutations such as BRAF^V600E^ and NRAS, lipid metabolic reprogramming has emerged as a critical factor in tumor progression and therapy resistance. Lipid metabolism supports melanoma cell survival, phenotypic switching, immune evasion, and resistance to targeted therapies and immunotherapy, while also modulating susceptibility to ferroptosis. This review summarizes current knowledge on lipid dysregulation in melanoma, highlighting alterations in fatty acid synthesis, desaturation, uptake, storage, and oxidation, as well as changes in phospholipids, sphingolipids, cholesterol, and bioactive lipid mediators. These lipid pathways are tightly regulated by oncogenic signaling networks, including MAPK and PI3K–AKT–mTOR pathways, and are influenced by tumor microenvironmental stressors such as hypoxia and nutrient limitation. Advances in lipidomics technologies, particularly mass spectrometry-based approaches, have enabled comprehensive profiling of lipid alterations at bulk, spatial, and single-cell levels, offering new opportunities for biomarker discovery and therapeutic stratification. Targeting lipid metabolic vulnerabilities represents a promising strategy to improve melanoma diagnosis, prognosis, and treatment efficacy.

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