Unraveling the Enigma of Melanoma Brain Metastasis: New Horizons in Mechanisms, Diagnosis, and Therapy

Melanoma, a highly aggressive and metastatic cancer, poses significant challenges due to its propensity to spread to distant organs, with brain metastasis representing a particularly devastating complication. This review synthesizes recent advances in understanding the molecular, cellular, and microenvironmental mechanisms driving melanoma metastasis, with a specific emphasis on brain metastasis. We explore the unique challenges of brain metastasis, including blood-brain barrier penetration, brain-specific microenvironment interactions, and genomic distinctions. Advances in diagnostic tools, such as imaging and liquid biopsies, are discussed alongside current and emerging therapeutic strategies, including novel small molecules, immunotherapies, and combination approaches tailored for brain metastases. The review also highlights the immunological landscape of the brain, translational models, and multidisciplinary clinical management strategies. Finally, we identify critical research gaps, including the need for brain metastasis-specific clinical trials, AI-driven predictive models, and preventive strategies, to guide future efforts in improving outcomes for patients with melanoma brain metastasis.