Walter Berger receives FWF Research Grant in the translational brain tumour research sector

Fibroblast Growth Factor Receptors (FGFR) are signal proteins which are involved in many growth and differentiation processes of healthy tissue. In the project, supported by the FWF with 401,000 Euro, the research group from the Medical University of Vienna led by Walter Berger examines the role played by FGFR4 in the glioblastoma, a malignant brain tumour in adults. The objective is to find out whether FGFR4 and the malignant signals activated by it could be an attractive therapeutic point of attack.

The glioblastoma is one of the most frequent brain tumours in adults. This disease is currently considered incurable, which is the reason for an intensive global quest to find new therapy approaches. The research group headed by Walter Berger at the Institute of Cancer Research deals with the molecular mechanisms of the origin and progression of glioblastomas. Berger is the deputy head of the Institute and the co-coordinator of the Central Nervous System Tumour Unit of the Comprehensive Cancer Center Vienna.

The researchers were able to demonstrate that inhibiting FGFR4 in two-dimensional cancer cell cultures has minimum effect, yet massively inhibits the growth of cancer cells in the clinically more relevant three-dimensional model (neurospheroid). It was also confirmed in the respective mouse model that a blockage managed to inhibit almost all growth processes. Although FGFR4 does not seem to be the driver mutation of the malignant cell growth, but should support and/or facilitate the three-dimensional growth.
Berger: "How FGFR4 accomplishes this is still unclear and the clarification of this issue is one of the research objectives of our project. Once we know the mechanisms for three-dimensional growth and the invasion, we can establish which functions prevent the advancement of the disease."

In the current work supported by the FWF, a multitude of models is established which permit specifically blocking FGFR4 and to examine the effects on the cancer development. In the process, the scientists are able to revert to a huge amount of human, living tumour material. Berger: "During the past years, we have been able to establish a large cell bank in cooperation with the clinics at the Vienna General Hospital and the Kepler University Linz, and now possess living cell cultures of approximately 1,000 tumour samples."
This makes it also possible for the research project to examine cell-biological functions of FGFR4 which could be involved in the invasiveness of the glioblastoma.

Besides the intracellular kinases function, meaning the ability to transmit signals in the cell, the parts of FGFR4 at the cell surface (extracellular domains) interact with adhesion molecules, which regulate the adhesion and detachment of cells. In addition, they interchange with protein-cutting molecules, such as the matrix metalloproteinases (MMP), which allow the "immigration" of tumour cells into healthy brain tissue. Early examinations showed that the FGFR4 particularly strongly activates a very aggressive form of MMP in liver carcinomas. Both functions, the regulation of the adhesion and the penetration of the extracellular matrix, are prerequisites for the invasiveness and thus the malignancy of the glioblastoma.

In the current project it is now investigated whether the inhibition of the kinases activity of FGFR4 (through gene manipulation or medicinal) is sufficient to reduce the malignant growth of glioblastoma or whether also the kinases-independent functions of FGFR4 that promote invasiveness can represent approaches for a targeted therapy.

Regarding FWF
The scientific funds FWF (Funds for the promotion of scientific research) is Austria's central institution for the promotion of fundamental research. It is aimed to promote the further development of the sciences at a high level and thus secure the scientific location.

Regarding the person
Walter Berger was born in Reichraming in Upper Austria in 1963. Following the completion of his biology and German philology studies, he worked as a project manager at Hoechst Austria for three years. His interest in science led him to return to research and write his dissertation at the Institute of Cancer Research. After his research period at the Cambridge University, UK, he habilitated in the topic of therapy resistance in oncology at the University ofVienna in 2001. In 2010, Berger was assigned deputy head of the Institute of Cancer Research of the Medical University of Vienna. In November 2013, he was appointed university professor for applied and experimental oncology at the Institute of Cancer Research (IKF) of the Medical University of Vienna. The cancer scientist is also an active member of the Comprehensive Cancer Center of the Medical University of Vienna and the Vienna and the Vienna General hospital.