The German Research Foundation (DFG) is supporting a highly innovative research project by Professor Alexander Kleger with a Reinhart Koselleck grant in the amount of 1.25 million euros. The Medicine Professor, who heads the Institute of Molecular Oncology and Stem Cell Biology at Ulm University Hospital, is researching a ground-breaking new approach to the development and early progression of pancreatic cancer. This involves the use of stem cell-based, artificial pancreases as well as new methods for recreating the tumour environment.
Pancreatic cancer is one of the deadliest types of cancer. A special form is known as pancreatic ductal adenocarcinoma, in which the glandular tissue itself is affected. "How such carcinomas develop, why they are so different and what triggers cancer formation in the first place is still largely unexplored," says Ulm pancreas researcher Professor Alexander Kleger. The physician is Director of the Institute of Molecular Oncology and Stem Cell Biology (IMOS) and also heads the Section for Interdisciplinary Pancreatology at the Department of Internal Medicine I. Kleger and his team have developed pancreatic organoids based on human pluripotent stem cells at his institute, which he hopes to use to clarify the pathophysiological relationships of early carcinogenesis. He is being supported by the German Research Foundation via the Reinhart Koselleck Programme with 1.25 million euros, the highest amount of this highly competitive funding line.
"This research project is not focussed on the late or final stages of cancer, but rather on uncovering precursor stages and identifying early events that play a role as cancer triggers," explains Kleger. More specifically, the project aims to find out how early events, together with genetic, epigenetic and environmental factors, affect tumour formation and development. What role do the original cell type or certain genetic mutations play? What influence do the cells of the microenvironment have on tumour development? How do environmental factors or a certain lifestyle contribute to the development of pancreatic cancer? These include, for example, factors such as alcohol, nicotine, diet or medication.
We are looking for biomarkers that provide notes on precursor stages
The overarching aim of the FIRE project - the acronym stands for "Fighting pancreatic cancer by origin and niche" - is to develop new diagnostic and therapeutic strategies for pancreatic cancer. This means that, on the one hand, the scientists involved in the project are looking for biomarkers that provide notes on precursor stages and thus help to improve early detection. Unfortunately, those affected often remain symptom-free for a long time, and by the time the first symptoms appear, the disease is usually already very advanced. On the other hand, the researchers hope to gain insights into the prevention and treatment of tumours at an advanced stage of the disease. "We need precise targets for the development of personalised therapies. Because every cancer is different," emphasises the Ulm pancreatic cancer expert.
"We are delighted that the German Research Foundation is supporting this project as part of this excellence funding programme. This is not only a significant success for Professor Alexander Kleger, who has already been awarded the German Cancer Prize in 2023, but it also demonstrates the outstanding position of Ulm as a research location," says a delighted Professor Thomas Wirth, Dean of the Medical Faculty at Ulm University. The Reinhart Koselleck Programme serves to promote particularly innovative and, in a positive sense, risky research. It is aimed at researchers who have demonstrated outstanding scientific service performances in their field. The prestigious programme is named after Reinhart Koselleck, one of the most important German historians of the 20th century. The funding period is five years.
How can early stages of cancer communicate with their environment?
What makes the project so unique is its pioneering methodology: "The protocols for the development of pancreatic organoids were developed at our institute from human pluripotent stem cells over many years. Like their natural model, they consist of different cell types, either acinar or ductal cells - both of which are the origin of pancreatic cancer. They can be genetically defined and thus biologically customised," explains Kleger. The Ulm researchers use an organ culture scaffold based on porcine urinary bladders for their prolonged culture and interaction with cells in their environment. In addition to the urinary bladder model, innovative cocultures and 3D bioprinting techniques are also used to investigate the interaction and communication between the tumour and its environment. The researchers want to find out which signal transmission pathways play a role in the early phase of tumour formation. Blocking such communication pathways could be used therapeutically in the future to better treat the tumour.
The novel culture model consisting of an artificial pancreas and tumour environment also helps to reduce animal testing. Ulm University is part of the 3R network funded by the state of Baden-Württemberg. The aim of this joint initiative is to replace, reduce and refine animal experiments.
The main work of the project takes place at IMOS. However, as the research project is very extensive, external cooperation partners are also involved: these include Professor Ivan Costa from the University of Aachen, Professor Roland Rad from the Technical University of Munich and Professor Gabriele Capurso from the Pancreas Centre in San Raffaele, Milan. Another cooperation partner is Dr Medhanie Mulaw from the Central Unit for Single Cell Sequencing at Ulm University.
Further information:
Univ.-Prof. Dr rer. med. Alexander Kleger
Director, Institute of Molecular Oncology and Stem Cell Biology
Section Head, Interdisciplinary Pancreatology, Department of Internal Medicine I
Ulm University Hospital, Email: alexander.kleger(at)uni-ulm.de
Explanatory film (5 min) of the German Stem Cell Network on the research of Prof Dr Alexander Kleger "With organoids against pancreatic cancer" by Scinelion
https://www.youtube.com/watch?v=qiOvVWsl_bw
Text (German) and media contact: Andrea Weber-Tuckermann