The response of cancer patients to a specific chemotherapy line can vary dramatically. The reasons for this are manifold and unknown for the most part. Scientists in the Analytical Pathology Department (AAP) of the Helmholtz Zentrum München have recently been successful in exposing a mechanism that is relevant to this phenomenon. Dr. Michaela Aichler and her colleagues have found out that the function of enzymes within the respiratory chain, which takes place in the mitochondria of cells, regulates the sensitivity of cells for cisplatin-based chemotherapeutic agents.
The scientists examined tissue, to this end, from tumours in the oesophagus, stomach and chest of a total of 428 patients. By means of an image-guided procedure (the so-called MALDI-Imaging and LC-MS/MS), protein patterns within the cells were able to be established and the illustrated enzymes identified. These patterns of existing and/or missing enzyme functions were compared by the scientists with the clinical response of the patients to a chemotherapy line containing cisplatin. If a defect was present in the respiratory chain complex within the tumour cells – particularly in subunits of the specific cytochrome c oxidase (COX) – an improvement in the effect of the chemotherapy could be observed. This correlation was able to be additionally proved in subsequent experiments with the tissue samples. When the COX function was missing, a quicker cell death was noted with the introduction of cisplatin or other related treatments. Conversely, cells with an intact respiratory chain proved to be resistant to the administered substances.
“Recognition of these correlations contributes to an improved ability to predict the efficacy of certain chemotherapies”, explains Prof. Dr. Axel Walch, Director of AAP. “It is possible that mitochondria, and/or their function enzymes, can be used in the future as biomarkers for personalised therapeutic approaches.”
The focus of health research at the Helmholtz Zentrum München is placed on serious widespread diseases. This includes diabetes, lung diseases as well as cancer. It is the goal of the Helmholtz Zentrum München to quickly refine results from basic research to provide society with concrete benefits.
Figure: Diagram of the response to cisplatin-based chemotherapies subject to the COX function.
Aichler, M. et al. (2013), Clinical response to chemotherapy in oesophageal adenocarcinoma patients is linked to defects in mitochondria, Journal of Pathology, doi: 10.1002/path.4199
As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,100 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 34,000 staff members. www.helmholtz-muenchen.de
The Analytical Pathology Department (AAP) carries out scientific development, as a complement to research units with a clinical and fundamental orientation, of translational research on diseases that occur in tissue. AAP is involved in the translation of (for example) in-vitro models or animal models to application in humans. AAP thus links, in collaboration with the Institute for Pathology (PATH), basic research with diagnostic application, subsequently translating the findings of experimental and molecular pathology into procedures for the classification of diseases and predictive diagnostics dealing with tissue.
Prof. Axel Walch, Helmholtz Zentrum München – Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Analytical Pathology Department, Ingolstädter Landstr. 1, 85764 Neuherberg – Tel.: 089-3187-3349 – E-Mail: axel.walch(at)helmholtz-muenchen.de