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Open AccessFeature PaperReview

Against Repurposing Methadone for Glioblastoma Therapy

1
Department of Radiation Oncology, University of Tübingen, 72076 Tübingen, Germany
2
Department of Pharmacology, Toxicology and Clinical Pharmacy, Institute of Pharmacy, University of Tübingen, 72076 Tübingen, Germany
3
German Cancer Consortium (DKTK), Partner Site Tübingen, Tübingen, Germany, and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(6), 917; https://doi.org/10.3390/biom10060917
Received: 11 May 2020 / Revised: 8 June 2020 / Accepted: 11 June 2020 / Published: 17 June 2020
(This article belongs to the Special Issue Repurposing Drugs for Anti-Cancer Therapy)
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. View Full-Text
Keywords: ionizing radiation; flow cytometry; cell cycle regulation; clonogenic survival; colony formation assay; human glioblastoma cell lines; T98G; A172; U87MG; U251 ionizing radiation; flow cytometry; cell cycle regulation; clonogenic survival; colony formation assay; human glioblastoma cell lines; T98G; A172; U87MG; U251
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MDPI and ACS Style

Vatter, T.; Klumpp, L.; Ganser, K.; Stransky, N.; Zips, D.; Eckert, F.; Huber, S.M. Against Repurposing Methadone for Glioblastoma Therapy. Biomolecules 2020, 10, 917.

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