Against Repurposing Methadone for Glioblastoma Therapy

• Published in: Biomolecules (Basel, Switzerland) Vol. 10; no. 6; p. 917
• Main Authors: Vatter, Tatjana, Klumpp, Lukas, Ganser, Katrin, Stransky, Nicolai, Zips, Daniel, Eckert, Franziska, Huber, Stephan M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.06.2020; MDPI
• Subjects: Addictions; Analgesics; Antineoplastic Agents - pharmacology; Brain cancer; Brain Neoplasms - drug therapy; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Cancer therapies; Care and treatment; cell cycle regulation; Cell death; Clinical trials; clonogenic survival; colony formation assay; Colorectal carcinoma; Drug dosages; Drug interactions; Drug Repositioning; Drug withdrawal; Enzymes; flow cytometry; Glioblastoma; Glioblastoma - drug therapy; Glioblastoma - metabolism; Glioblastoma - pathology; Glioblastoma cells; Glioblastoma multiforme; human glioblastoma cell lines; Humans; ionizing radiation; Medical prognosis; Metabolism; Metabolites; Methadone; Methadone - pharmacology; Morphine; Narcotics; Opioids; Patient outcomes; Patients; Permeability; Pharmacokinetics; Radiation therapy; Radioresistance; Receptors, Opioid, mu - agonists; Receptors, Opioid, mu - metabolism; Review; Germany; United States > US; human glioblastoma cell lines; T98G; colony formation assay; A172; U87MG; flow cytometry; cell cycle regulation; U251; ionizing radiation; clonogenic survival
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom10060917

Methadone, which is used as maintenance medication for outpatient treatment of opioid dependence or as an analgesic drug, has been suggested by preclinical in vitro and mouse studies to induce cell death and sensitivity to chemo- or radiotherapy in leukemia, glioblastoma, and carcinoma cells. These data together with episodical public reports on long-term surviving cancer patients who use methadone led to a hype of methadone as an anti-cancer drug in social and public media. However, clinical evidence for a tumoricidal effect of methadone is missing and prospective clinical trials, except in colorectal cancer, are not envisaged because of the limited preclinical data available. The present article reviews the pharmacokinetics, potential molecular targets, as well as the evidence for a tumoricidal effect of methadone in view of the therapeutically achievable doses in the brain. Moreover, it provides original in vitro data showing that methadone at clinically relevant concentrations fails to impair clonogenicity or radioresistance of glioblastoma cells.