New research alliance investigates resistance to treatment in colorectal cancer

Colorectal cancer is curable, if it is detected early and can be completely removed surgically. The situation becomes more difficult in advanced stages of the disease. Immunotherapies that activate the body‘s own defence system are considered promising in this context. However, they are only effective in about one in six patients. The new TRR 417 Collaborative Research Centre is therefore dedicated to researching the tumour microenvironment; that is, the network of cells in which tumour cells grow. The aim is to modify this environment in a targeted manner to make treatments more effective. The alliance, which is funded by the German Research Foundation (DFG), is led by Goethe University Frankfurt. Both the University of Freiburg and the Friedrich-Alexander-Universität Erlangen-Nürnberg are also involved.

“Tumours are not isolated collections of cells – they interact closely with their environment. This microenvironment can significantly impair the effectiveness of treatments, especially in the case of metastases in the liver and peritoneum. This is exactly where we come in,” says Prof. Dr. Stefan Fichtner-Feigl, member of the Medical Faculty of the University of Freiburg and Medical Director of the Department of General and Visceral Surgery at the Medical Centre – University of Freiburg. “The funding for TRR 417 is a valuable recognition of our work. It gives us the opportunity to find new ways to offer hope to patients with tumours that have been resistant to treatment until now.”

“We are delighted to receive this research funding. It shows that only through close networking and mutual exchange can we achieve progress that will improve the treatment of colorectal cancer, thereby helping our patients,” says Prof. Dr. Lutz Hein, Dean of the Faculty of Medicine at the University of Freiburg.

“We are delighted to receive this research funding. It shows that only through close networking and mutual exchange can we achieve progress that will improve the treatment of colorectal cancer, thereby helping our patients.”

Prof. Dr. Stefan Fichtner-Feigl

Member of the Medical Faculty of the University of Freiburg and Medical Director of the Department of General and Visceral Surgery, Medical Centre University of Freiburg

Why only a few intestinal tumours respond to immunotherapy

Approximately 10 to 15 percent of colon tumours respond well to modern immunotherapies. So-called immune checkpoint inhibitors are often used to disable the tumour’s protective mechanisms. This makes the tumour ‘visible’ to the immune system, allowing the body’s own defence cells – T cells – to target the cancer cells.

However, immunotherapies have so far had little effect on the majority of colorectal cancer patients. Even traditional treatment approaches such as chemotherapy and radiotherapy often reach their limits in these cases. The reason for this is the complex tumour microenvironment: a dynamic environment consisting of connective tissue cells (fibroblasts), immune cells, blood vessels and intestinal microorganisms. These so-called stromal cells are manipulated by the tumour and unintentionally support its growth and resistance to therapies.

Collaboration between medicine, biology and data sciences

In the new Collaborative Research Centre/Transregio TRR 417 “Cellular Communication in the Stroma of Colorectal Cancer: From Pathophysiology to Clinical Translation,” researchers from medicine, biology and data sciences are pooling their expertise. “We want to find out how we can specifically modify the tumour microenvironment and use it therapeutically to improve treatments and make them accessible for immunotherapies – especially for colon tumours, which have responded poorly to existing therapies thus far,” says Prof. Dr. Florian Greten, cancer researcher at the Georg Speyer House and Goethe University Frankfurt and spokesperson for the new TRR 417.