How can gastrointestinal stromal tumors - GIST - be treated and new therapies developed? The research groups of Prof. Daniel Rauh from the Department of Chemistry and Chemical Biology at TU Dortmund University and Prof. Sebastian Bauer from the West German Cancer Center in Essen are investigating these questions together.

The oncologists from Essen and the drug researcher from Dortmund have been researching GIST for more than ten years. Together, they have now gained new insights into the molecular mechanisms behind resistance mutations in this rare gastrointestinal tumor: Their findings have been published in “Nature Communications” and in the “Journal of Clinical Oncology”.

Led by Prof. Sebastian Bauer from the Department of Medicine at the University of Duisburg-Essen, the researchers identified a novel resistance mechanism that explains why GIST patients fail to respond to current therapies. This work, published in the Journal of Clinical Oncology, is essential for the development of new treatments. The second study, led by Prof. Daniel Rauh (photo) and published in Nature Communications, focuses on the binding mode of the newly approved drug “avapritinib”. Resistance mutations occurred after only a short time with this drug. The study provides important insights for the development of innovative drugs to circumvent this resistance.

Both publications are the result of a close collaboration between oncologists in Essen and drug researchers in Dortmund. Prof. Bauer and his team work primarily clinically: he treats GIST patients and develops genetic tumor models that can be used to study drug resistance. Prof. Rauh and his team are investigating the molecular causes of these resistance mutations. Using protein X-ray crystallography, structure analysis, and preparative organic synthesis, the researchers are developing small molecule inhibitors that may bypass resistance in GIST and provide new starting points for drug development.

The research work was supported by the EU, the German Research Foundation (DFG), the state of North Rhine-Westphalia, and the Mercator Research Center Ruhr (MERCUR). They are embedded in the Drug Discovery Hub Dortmund (DDHD), the CANTAR research network, and the MERCUR project IGNITE.