Methadone against cancer: Lost in translation
Recently, the opioid analgesic d,l-methadone has gained much attention as a potential antineoplastic compound, considerably triggered through lay press and media. In consequence, physicians and pharmacists are currently confronted with numerous patients willing to use d,l-methadone against their mal...
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| Hauptverfasser: | , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
08 March 2018
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| In: |
International journal of Cancer Studies & Research
Year: 2018, Jahrgang: 143, Heft: 8, Pages: 1840-1848 |
| ISSN: | 2167-9118 |
| DOI: | 10.1002/ijc.31356 |
| Online-Zugang: | Verlag, Volltext: https://doi.org/10.1002/ijc.31356 Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.31356 |
| Verfasserangaben: | Dirk Theile and Gerd Mikus |
| Zusammenfassung: | Recently, the opioid analgesic d,l-methadone has gained much attention as a potential antineoplastic compound, considerably triggered through lay press and media. In consequence, physicians and pharmacists are currently confronted with numerous patients willing to use d,l-methadone against their malignancies. Well-performed in vitro and in vivo models have in fact shown pro-apoptotic effects of d,l-methadone or other opioids, but also proliferation-stimulating properties. Moreover, the mechanisms of proposed opioid-stimulated apoptosis are incompletely described or contradicting. Finally, the receptors mostly responsible for induction of apoptosis by d,l-methadone remain unclear as contributions of both µ-opioid receptors, Fas cell death receptors, toll-like receptors, N-Methyl-d-aspartate receptors and opioid growth factor receptors were suggested. Such ambiguity prevents rational application of d,l-methadone or patient stratification to enhance beneficial antineoplastic effects. From a clinical point of view, d,l-methadone and other opioids might in fact prolong survival, but such effects likely originate from their analgesic and neuro-psychotropic properties and, thus, improvements of quality of life. Crucial obstacles to the administration of d,l-methadone are incomplete knowledge about its systemic disposition, highly variable pharmacokinetics, profound drug-drug- or drug-disease interaction and QT-prolongation potential. This article summarizes and rates the pharmacological basis of d,l-methadone as an antineoplastic agent and puts its administration in clinical oncology into perspective. Despite enthralling experimental findings about d,l-methadone-mediated apoptosis in cancerous cells or tissues, clinicians should realize the current lack of evidence for the use of d,l-methadone as an antineoplastic agent. Its administration against cancer pain is, however, tenable, albeit restricted to certain clinical situations. |
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| Beschreibung: | Gesehen am 05.08.2019 |
| Beschreibung: | Online Resource |
| ISSN: | 2167-9118 |
| DOI: | 10.1002/ijc.31356 |