Zusammenfassung
Der vorliegende Beitrag fasst Ergebnisse der experimentellen und der klinischen Onkologie zusammen, die auf eine zentrale Bedeutung des Kohlenhydratstoffwechsels maligner Tumoren für Malignitätsgrad und Therapieansprechen hinweisen. In Primärtumoren, wie etwa in Zervixkarzinomen, Plattenephithelkarzinomen der Kopf-Hals-Region oder Adenokarzinomen des Rektums, ist bereits bei Erstdiagnose eine überdurchschnittliche Laktatakkumulation als Spiegel einer hohen Glykolyseaktivität mit erhöhter Metastasenbildung oder höherer Strahlenresistenz verknüpft. Der Zusammenhang zwischen therapeutischer Resistenz und Glykolyse beruht zumindest teilweise auf den Radikalfängereigenschaften glykolytischer Produkte, hauptsächlich Pyruvat und Laktat, sowie deren Verknüpfung mit dem Redoxstatus der Zelle. Vor diesem Hintergrund wurde das neue Verfahren der quantitativen Biolumineszenz zur bildgebenden Darstellung des Laktat/Pyruvat-Verhältnisses in Tumorbiopsien entwickelt. Künftige Forschungsinitiativen in der Onkologie sollten vermehrt auf den Redoxstatus solider Tumoren fokussieren.
Abstract
This article summarizes data from experimental and clinical oncology which are indicative of a pivotal role of tumor carbohydrate metabolism in malignant behavior and outcome of treatment. In primary tumors, such as cervix carcinomas, head and neck squamous cell carcinomas or rectum adenocarcinomas, elevated lactate levels as a mirror of a high glycolytic activity, are correlated even at the initial diagnosis with a high level of malignancy as indicated by increased formation of metastases or an elevated radiotherapy resistance. The relationship between therapeutic resistance and glycolysis may at least partially be due to the radical scavenging potential of glycolytic intermediates, mainly pyruvate and lactate and to the link between these metabolites and the cellular redox status. On the basis of these data and other considerations, a novel technique has been developed for imaging the lactate/pyruvate ratio in tumor biopsies using quantitative bioluminescence. More research effort should, therefore, be focussed on the redox status of tumors in oncological studies in the future.
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Wir danken der Deutschen Forschungsgemeinschaft (Mu 576/14–1, 14–2 und 14–3) und der Stiftung Rheinland-Pfalz für Innovation (15202–386261/606) für die Unterstützung.
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Gewidmet Herrn Prof. Dr. med. Rolf Zander für die jahrzehntelange Zusammenarbeit im Physiologischen Institut.
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Sattler, U., Walenta, S. & Mueller-Klieser, W. Laktat und Redoxstatus in malignen Tumoren. Anaesthesist 56, 466–469 (2007). https://doi.org/10.1007/s00101-007-1164-2
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DOI: https://doi.org/10.1007/s00101-007-1164-2