Boron Neutron Capture Therapy in Cutaneous Melanoma: Novel Delivery Strategies

Abstract

Cutaneous Melanoma (CM), with its profound heterogeneity and capacity for therapy resistance, represents a persistent challenge in oncology. This review charts the evolution of management strategies from a refined understanding of molecular pathogenesis towards the advent of highly selective therapeutic modalities. While the foundation of modern care rests on targeting key oncogenic pathways and integrating advanced diagnostics such as PRAME and liquid biopsies, a significant development lies in the application of Boron Neutron Capture Therapy (BNCT). This binary modality achieves exceptional micro-scale selectivity through biochemical targeting, with clinical data confirming its efficacy against radioresistant disease. The forthcoming transformation in BNCT efficacy and accessibility is increasingly linked to innovations in two key areas: the transition to compact accelerator-based neutron sources and, crucially, the rational design of novel boron delivery agents. This work provides a critical analysis of the paradigm shift from low-molecular-weight compounds towards sophisticated nanoscale systems. A particular focus is placed on hyaluronic acid-based platforms engineered for active targeting via the CD44 receptor, as well as on groundbreaking approaches like elemental boron nanoparticles. The emergence of these novel constructs signals a progression towards more precise and personalized oncologic interventions. To provide a comprehensive overview, this article is structured to first examine the molecular and diagnostic landscape of cM, then detail the principles and clinical evidence for BNCT, and finally analyze the cutting-edge strategies for boron delivery, concluding with future perspectives. Thus, BNCT, augmented by these advanced delivery technologies, is positioned as a compelling and precise approach for addressing the central challenge in CM: Overcoming therapy resistance.