A New Era of Proactive Melanoma Therapy: Hit Hard, Hit Early

L. Haas; T. Wiesner; A. C. Obenauf


The British Journal of Dermatology. 2018;178(4):817-820. 

In This Article

Future Directions: Combination of Targeted and Immunotherapies

Despite tremendous progress and numerous therapeutic options, half of all metastatic melanoma patients still die of their disease. Biomarkers for prognosis, responsiveness and resistance will be critical to better stratify patients according to their therapeutic needs. Even more importantly, there is a growing body of evidence that the combinations of drugs can significantly enhance response rates and long–term tumour control.[19] For example, the potency of checkpoint inhibitors could be enhanced by the inhibition of immunosuppressive signals (for example indoleamine 2,3–dioxygenase or CD73) or of oncogenic pathways that exert immunosuppression in the tumour microenvironment (for example the Wnt or MAPK pathway).[13,20,21] The efficacy of MAPK pathway inhibitors in combination with immune modulators is already substantiated by numerous preclinical and clinical studies.[19,22] A better understanding of the reciprocal interactions and synergies of individual drugs will be critical to identify more effective treatment combinations and schedules, and ultimately exploit these exciting new drugs to their full potential.