D,L-Methadon erhöht den zytotoxischen Effekt konventioneller Krebstherapien

Zusammenfassung

Resistenzen gegenüber konventionellen Behandlungsmethoden limitieren den Erfolg in der Krebstherapie. Dies fordert, neue Therapiestrategien zu entwickeln, um den therapeutischen Erfolg zu verbessern. Krebszellen exprimieren auf ihrer Zelloberfläche sehr stark Opioidrezeptoren. Dies ermöglicht Opioiden, an die Krebszelle zu binden.

Methadon, das an Opioidrezeptoren bindet und in der Schmerztherapie bei Tumorpatienten eingesetzt wird, hat in vitro und im Mausmodell in vivo gezeigt, dass Chemotherapeutika in ihrer zytotoxischen Wirkung verstärkt werden können. Über die Aktivierung des Opioidrezeptors und die Herunterregulation von zyklischem Adenosinmonophosphat (cAMP) kann D,L-Methadon Apoptose-Signalwege aktivieren und antiapoptotische Moleküle, die zur Therapieresistenz führen können, blockieren. Des Weiteren kann D,L-Methadon zur einer stärkeren Aufnahme des Chemotherapeutikum in der Tumorzelle führen. Hierbei kommt es auf die Expression der Opioidrezeptoren auf der Oberfläche der Tumorzellen an. Bei einer starken Expression kann D,L-Methadon sogar allein den Zelltod in der Tumorzelle auslösen. Bei einer moderaten Expression verstärkt D,L-Methadon konventionelle Therapien in ihrer zytotoxischen Wirkung. Gesundes Gewebe, das wenig oder keine Opioidrezeptoren exprimiert, wird von der zytotoxischen Verstärkung von D,L-Methadon verschont. In einer retrospektiven klinischen Studie zur Behandlung von Gliomen wurde gezeigt, dass D,L-Methadon ohne erhebliche oder toxische Nebenwirkungen zusätzlich bei der Behandlung von Gliomen eingesetzt werden kann.

ABSTRACT

Resistance to conventional treatment methods limits the success in cancer therapy. This calls for new therapies to develop strategies to improve therapeutic success. Cancer cells express very strongly opioid receptors on their cell surface. This allows opioids to bind to the cancer cell.

Methadone, which binds to opioid receptors and is used in pain therapy in tumor patients, has shown in vitro and in the mouse model in vivo that chemotherapeutic agents can be enhanced in their cytotoxic effect. By activating the opioid receptor and downregulating cyclic adenosine monophosphate (cAMP), D, L-methadone can activate apoptotic signaling pathways and block antiapoptotic molecules that can lead to resistance to cancer therapy. Furthermore, D, L-methadone can lead to a stronger uptake of the chemotherapeutic agent in the tumor cell. The expression of the opioid receptors on the surface of the tumor cells depends on this. In the case of strong expression of opioid receptors, D, L-methadone can even trigger cell death in the tumor cell alone. With moderate expression of opioid receptors, D, L-methadone enhances conventional cytotoxic effects. Healthy tissue that expresses little or no opioid receptors is spared by the cytotoxic enhancement of D, L-methadone. In a retrospective clinical study for the treatment of gliomas, it has been shown that D, L-methadone can also be used in the treatment of gliomas without significant or toxic side effects.

Schlüsselwörter

Methadon - Chemotherapie - Krebs - Resistenz - Krebstherapie - Opioidrezeptor

Key words

methadone - chemotherapy - cancer - resistance - cancer therapy - opioid receptor

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