Wir überwinden Grenzen

US funding for a project at the Medical Center - University of Freiburg that sheds light on the connection between microbial degradation products in the intestine and the development of cancer at the junction between the esophagus and stomach / Only grant

With a high-fat diet, the bacteria in the intestine increasingly produce so-called secondary bile acids as a breakdown product. A major research project now aims to clarify whether and how these bile acids promote cancer at the junction between the oesophagus and stomach in its earliest stages and whether targeted microbial therapy can reduce the risk of cancer. It is being funded by the US National Institutes of Health (NIH) as part of the US consortium "Program on the Origins of Gastroesophageal Cancers". The only one of the eight approved sub-projects that is not based in the USA is being led at the Medical Center - University of Freiburg and will be funded for five years from January 2023 with the equivalent of around 1.2 million euros.

"We want to better understand how cancer develops in the oesophagus and adjacent areas of the stomach. This research project offers the opportunity to take a major step forward in the search for causes, treatment and prevention of gastric and esophageal cancer," says study leader Prof. Dr. Michael Quante, Head of the Division of Gastrointestinal Oncology at the Department of Medicine II at the Medical Center - University of Freiburg.

In Germany, more than 7,000 people are diagnosed with esophageal cancer every year. Some of these are gastroesophageal tumors, which are the subject of this project. To date, little is known about the causes of the development of these tumors, so there is no targeted therapy. The cure rate is also low.

Stem cells in a delicate balance

Together with project partners from Columbia University, USA, Quante wants to elucidate the molecular mechanisms by which secondary bile acids affect stem cells in the transition zone between the oesophagus and stomach and how they trigger pathological changes. Quante and his team discovered a few years ago that these stem cells play an important role in the development of cancer. "The stem cells are in a delicate balance: in a normal state, they are responsible for the continuous renewal of the oesophageal surface. If cell renewal is too low, food transport would be jeopardized, and if renewal is too high, cancer cells can develop. We want to find out how secondary bile acids shift this balance," explains Quante.

"This funding is a strong sign of the international competitiveness of university medicine in Freiburg. It shows the importance and prestige of the intensive interlinking of research and treatment that is unique to university hospitals," said Prof. Dr. Lutz Hein, Dean of the Faculty of Medicine - University of Freiburg and member of the Board of Directors of the Medical Center - University of Freiburg.

Understanding inflammatory processes in organoids

In the research project that is now starting, the Freiburg and US scientists will investigate the connections using so-called organoids, i.e. pieces of tissue grown in the laboratory, as well as mouse models established by Quante and patient samples. "The secondary bile acids are formed in the intestine by the microbiome and then enter the stomach and oesophagus via the blood. We suspect that they cause inflammation there, resulting in excessive activation of the stem cells. If we understand the very early signaling pathways better, we can also look for therapies, such as a change in the microbiome, that specifically intervene here," says Quante.

Website of the US consortium:www.cancer.gov/about-nci/organization/dcb/research-programs/gej

Contact:
Prof. Dr. Michael Quante
Head of the Center for Gastrointestinal Oncology
Department of Medicine II (focus: gastroenterology, hepatology, endocrinology and infectiology)
Medical Center - University of Freiburg
Phone: 0761 270-32768
michael.quante@uniklinik-freiburg.de