Plasma-Activated Liquid Modulated the Efficacy and Resistance of Targeted Therapy Agents in Melanoma Cells With BRAFV600E Mutation

Targeted therapy is the first-line treatment for melanoma patients harboring the BRAFV600E mutation. However, the development of drug resistance significantly limits its clinical efficacy and long-term patient survival benefits. Cold atmospheric plasma (CAP) has emerged as a promising adjunctive oncotherapy. Plasma-activated liquid (PAL), the indirect application of CAP, exhibits superior tissue penetration capabilities and has been extensively investigated in animal models. Previous study from our group indicated that PAL can sensitize melanoma cells to targeted therapeutic agents in vitro. However, therapeutic efficacy has not yet been evaluated in animal models. This study aimed to evaluate the combined effect of PAL and targeted therapy in BRAFV600-mutant melanoma both in vitro and in vivo. Results demonstrated that PAL enhanced the efficacy of targeted therapy and sensitized A2058 cells to the BRAF inhibitor GSK2118436. Furthermore, the combination of intratumoral PAL injection with targeted therapy significantly inhibited the growth of subcutaneous melanoma tumors in vivo. In conclusion, our findings suggest that PAL represents a novel and promising combined strategy for melanoma treatment.