FRANKFURT. In the realm of colorectal cancer treatments beyond surgery and radiation, one key question gained prominence in recent years: Is the tumor’s DNA repair system defective, making it “microsatellite unstable”? Around 15 to 20 percent of all tumors have this trait, making them likely candidates for successful immunotherapy. So-called immuno-checkpoint inhibitors are often used in these cases to neutralize the tumor’s “protective shield”, which tricks the immune system into perceiving it as harmless tissue. Once this deception is lifted, the body’s T-cells can eliminate the tumor.
However, many colorectal cancers remain resistant to immunotherapy and even to chemotherapy and radiation. The cause lies in the tumor’s surrounding environment, explains Prof. Florian Greten, cancer researcher at Georg-Speyer-Haus and Goethe University Frankfurt, and TRR 417 spokesperson: “Tumors do not grow as foreign bodies within intestinal tissue. Instead, they incorporate ‘normal’ cells such as fibroblasts, immune cells, and vascular cells. The tumor reprograms these cells and integrates them into a tumor microenvironment, which also closely interacts with gut bacteria and other microorganisms – the microbiome.”
The new Collaborative Research Center TRR 417 “Cellular Communication in the Stroma of Colorectal Cancer: From Pathophysiology to Clinical Translation” brings together researchers from medicine, biology, and data sciences at Goethe University Frankfurt, Friedrich-Alexander University Erlangen-Nuremberg, and the University of Freiburg with the aim of continuing the investigation of this tumor microenvironment. Greten explains: “We are building on the experience we’ve gained since 2016 through our collaboration in DFG Research Unit 2438 on this topic. In that project, we not only gathered numerous scientific insights but also developed shared standards, models, and technologies.” It is based on this foundation that the researchers will now develop novel therapeutic strategies. “We want to determine how to deliberately modify the tumor microenvironment and leverage it therapeutically to enhance treatments and make them accessible to immunotherapies – especially for those colorectal cancers that currently respond poorly to existing therapies.”
Goethe University President Prof. Enrico Schleiff: “The success of TRR 417 is particularly gratifying because it shows how Prof. Greten and his colleagues have strategically brought together top-tier oncology experts from leading institutions – German Cancer Aid, the German Cancer Consortium for Translational Cancer Research, the Bavarian Cancer Research Center, and the National Center for Tumor Diseases – over many years. Their approach of rapidly transferring basic research into clinical practice is a model for Goethe University’s ‘Science for Health’ profile area. I look forward to the rich scientific output and the next generation of clinician scientists that will emerge out of this collaborative research center.”
The DFG will fund TRR 417 for an initial period of four years with around € 17.7 million. The funding may be renewed twice for additional four-year periods.