The aim of the MSTARS consortium is to further develop current technology for clinical application and for the detection and classification of treatment resistance.The Federal Ministry of Education and Research (BMBF) will provide approximately €5.7 million in funding for a minimum of three years.
For many years, comprehensive genetic analysis was considered the method of choice in our attempts to better understand diseases such as cancer and provide patients with increasingly personalized treatment options. It was a successful approach which resulted in a myriad of new, targeted forms of treatment. “However, it was known from an early stage that the course of a disease is not solely determined by our genes,” explains one of the project’s four coequal coordinators, Professor Ulrich Keilholz, Director of the Charité Comprehensive Cancer Center (CCCC). “Instead, it is often determined by the extent to which these genes are translated into proteins, how the resulting proteins interact with one another, and how the disease affects our metabolism. Mass spectrometry enables us to identify and quantify biomolecules quickly and comprehensively. We will therefore use this technology to better understand the interplay of disease-relevant cell components and, by doing so, improve precision medicine, i.e. our ability to tailor treatments to the individual patient.”
Berlin expertise on mass spectrometry
The MSTARS consortium’s other three coordinators are Professor Matthias Selbach, Group Leader of the Proteome Dynamics Lab at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Proferssor Markus Ralser, Director of Charité’s Institute of Biochemistry, and Professor Frederick Klauschen of Charité’s Institute of Pathology. The project’s research partners include numerous other experts from Charité and the MDC, as well as scientists from the Berlin Institute of Health (BIH), Humboldt-Universität zu Berlin and the Max Planck Institute for Molecular Genetics. “By establishing this new research core, we are gathering all Berlin-based expertise on mass spectrometry, patient care and data analysis, and placing it under one roof,” says Selbach. “Combining the skills and experience of the various institutions and disciplines with Charité’s extensive clinical expertise will enable us to further develop mass spectrometry-based technologies and apply them in clinical practice.”
“A major aim in this regard is to make mass spectrometry-based methods even more robust and reproducible,” reflects Ralser and adds: “In order for this technology to improve patient care, we also need to be able to analyze large numbers of samples within a short time. To achieve this, we will build capacity and develop standardized procedures for all processes, from sampling through to data management.”
Same genes, different drug effect
The infrastructure which the consortium is planning to develop will be suitable for carrying out analyses on a vast array of disorders. The consortium’s research groups will start by studying treatment resistance in patients with squamous cell carcinoma of the head and neck. “The modern treatment strategies available for these patients mainly target specific genetically-determined dysfunctions present in an individual patient’s cancerous tissue,” says Klauschen. “For reasons which remain unexplained, these treatments will work very well in some patients but show no effect in other people with the same genetic makeup. We want to study patients’ tissue samples using mass spectrometry to distinguish these groups of patients and make it easier to decide whether or not a particular treatment should be used in a specific patient.” Doing so will require the analysis of vast quantities of data. Therefore, the researchers will also be using artificial intelligence-based approaches.
The MSTARS (Multimodal Clinical Mass Spectrometry to Target Treatment Resistance) project is being funded under a special BMBF funding program, which focuses on establishing research cores dedicated to mass spectrometry in systems medicine (‘Forschungskerne für Massenspektrometrie in der Systemmedizin’). MSTARS is one of a total of four such BMBF-funded consortia. Other research cores will be developed in Heidelberg, Mainz and Munich. Funding has been awarded for an initial period of three years. An interim review after two and a half years will determine whether project funding is to be extended for a further three years. The projects will be launched on 1 March 2020.
Mass spectrometry is an analytical technique used to measure the mass of molecules and atoms. The substance to be analyzed is first converted into gas-phase molecules which are subsequently converted into ions. Once accelerated to high velocity by an electrical field, these ions are then sorted by the mass spectrometer system’s analyzer and separated according to their mass/charge ratios. The resulting mass spectrum provides information on a substance’s molecular composition. Mass spectrometry is suitable for the identification, characterization and quantification of a myriad of biomolecules such as proteins, metabolites, sugars and fats, all of which behave differently depending on the precise clinical picture which manifests in a particular patient.
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Dr. Gina Dörpholz
Charité Comprehensive Cancer Center
Charité – Universitätsmedizin Berlin
+49 30 450 564 619
Prof. Dr. Matthias Selbach
Head of “Proteom-Dynamik“
Max Delbrück Center for Molecular Medicine (MDC)