Methadone-Not a magic bullet in melanoma therapy

Methadone (Met) mainly acts as a μ-opioid receptor agonist. Recent evidence pointing towards the role of Met in sensitization of certain cancer cell lines to chemotherapeutic agents has promoted the hypothesis that Met may be a useful adjuvant to cancer chemotherapy. We wanted to address whether Met has, alone or in combination with a chemotherapeutic agent, an effect on melanoma cell viability in vitro. Only a small fraction (4.3%) of our 102 melanoma biobank cell lines with RNA-sequencing data showed expression of the main receptor for Met (OPRM1). We assessed the viability of melanoma cell lines with high, medium or low/no OPRM1 expression (OPRM1^high , OPRM1^med , OPRM1^neg ) 72 hours after treatment with Met alone or combined with cisplatin (Cis). Our analyses show that Met alone did not affect cell viability. While Cis/Met treatment did not have an effect on viability of OPRM1^med or OPRM1^neg cell lines, it resulted in a slightly decreased cell viability of OPRM1^high cells. Clinically, concurrent temozolomide/Met treatment did not have an effect in our single-case report of a patient suffering from uveal melanoma. Taken together, our findings do not provide evidence for recommending Met as an adjuvant to chemotherapy in patients with melanoma.