Tyrosinase inhibitors as melanoma sensitizers: Boosting therapeutic efficacy

Melanoma therapy faces critical challenges due to melanin-mediated resistance mechanisms. The use of tyrosinase inhibitors to suppress tyrosinase activity and reduce melanogenesis, thereby sensitizing melanoma cells, represents a highly promising strategy for adjuvant melanoma therapy. However, most current review articles on tyrosinase inhibitors are primarily focused on discussing molecular inhibitor design and their depigmentation effects, while comprehensive reviews addressing their melanoma-sensitizing potential remain scarce. In this review, we systematically summarized recent development of tyrosinase inhibitor-mediated melanoma therapeutic treatment. Firstly we introduced the inhibiting mechanism of tyrosinase inhibitors and their development with various chemical structures and supramolecular assembly strategy. Then the tyrosinase inhibitor sensitization to irradiation/photodynamic therapy, chemotherapy, and immunotherapy was reviewed in detail, respectively, where the unique role of tyrosinase inhibitor in these therapeutic schemes are highlighted. Finally, we discuss potential optimization strategies for employing tyrosinase inhibitors in melanoma sensitization. This review timely addresses the critical gap in literature regarding tyrosinase inhibitor-mediated melanoma sensitization. It not only provides perspectives for clinical melanoma treatment but also facilitates the expansion of tyrosinase inhibitors' biomedical applications, thereby advancing the development of next-generation tyrosinase-targeted therapeutics.