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Against Repurposing Methadone for Glioblastoma Therapy
Tatjana Vatter1, Lukas Klumpp1, Katrin Ganser1
1Department of Radiation Oncology, University of Tübingen, 72074 Tübingen, Germany.
Biomolecules
|June 21, 2020
Summary
Methadone, used for opioid dependence and pain, shows preclinical anti-cancer promise. However, clinical data is lacking, and new research indicates it does not enhance glioblastoma cell death or radioresistance at relevant doses.
Area of Science:
- Oncology
- Pharmacology
- Neuro-oncology
Background:
- Methadone is used for opioid dependence and pain management.
- Preclinical studies suggest methadone may have anti-cancer effects, inducing cell death and sensitizing cancer cells to therapy.
- Public media has promoted methadone as an anti-cancer agent, fueled by anecdotal reports.
Purpose of the Study:
- To review methadone's pharmacokinetics and molecular targets in cancer.
- To evaluate the evidence for methadone's tumoricidal effect at clinically relevant brain concentrations.
- To present new in vitro data on methadone's effect on glioblastoma cells.
Main Methods:
- Literature review of methadone's pharmacokinetic and molecular properties related to cancer.
- Analysis of existing preclinical and clinical data on methadone's anti-cancer effects.
- In vitro experiments assessing methadone's impact on glioblastoma cell clonogenicity and radioresistance.
Main Results:
- Preclinical data suggests potential anti-cancer activity, but robust clinical evidence is largely absent.
- Methadone's pharmacokinetic profile allows for therapeutically relevant concentrations in the brain.
- In vitro studies demonstrated that methadone at clinically relevant concentrations did not impair glioblastoma cell clonogenicity or radioresistance.
Conclusions:
- Despite preclinical suggestions and public hype, there is a lack of clinical evidence supporting methadone's efficacy as an anti-cancer drug.
- Current in vitro data indicates methadone does not enhance the efficacy of standard cancer treatments like radiotherapy in glioblastoma.
- Further clinical investigation, beyond specific trials like in colorectal cancer, is not strongly supported by available preclinical and in vitro data.
