Award for pioneering findings on brain tumors
Scientists from Heidelberg University, Heidelberg University Hospital and the German Cancer Research Center have discovered how nerve cells in the brain get in contact with glioblastoma tumor cells and thus fuel their spread. The team has now been honored by the Portuguese BIAL Foundation with the highly endowed "BIAL Award in Biomedicine". The scientists will receive the award today at a ceremony in Lisbon from the hands of the Portuguese Minister of Health.
The findings of the Heidelberg scientists shed new light on the interaction between brain tumors and nerve tissue: healthy nerve cells in the brain get in contact with the tumor cells of glioblastomas and thus drive the growth of these incurable brain tumors. For these groundbreaking findings, published in Nature in 2019, the team led by Varun Venkataramani, Frank Winkler and Thomas Kuner, researchers at the Heidelberg Medical Faculty of Heidelberg University, will receive the BIAL Award in Biomedicine on February 20, 2024. The 300,000 euro prize is awarded every two years by the Portuguese BIAL Foundation and recognizes a scientific discovery in the field of biomedicine of exceptional quality and scientific relevance.
The Heidelberg scientists will receive the prize from the hands of Portuguese Minister of Health, Manuel Pizarro, at a ceremony this evening, also on behalf of all 29 co-authors of the article. Watch the livestream here from 7 pm.
Glioblastomas are highly aggressive tumors of the brain and are currently incurable. Patients usually die within two years despite intensive treatment with surgery, chemotherapy and radiotherapy. The team led by Frank Winkler, research group leader in the Clinical Cooperation Unit Neurooncology at Heidelberg University Hospital (UKHD) and the German Cancer Research Center, discovered one reason for this back in 2015: the glioblastoma cells are connected to each other by long cell extensions and grow into the healthy brain like a fungal network. On the one hand, this network cannot be surgically removed; on the other hand, the cells exchange important substances via these connections and thus protect themselves from the damage caused by the therapy.
During his research in the laboratories of Frank Winkler and Thomas Kuner, Head of the Department of Functional Neuroanatomy at the Institute of Anatomy and Cell Biology, Varun Venkataramani revealed the healthy nerve cells of the diseased brain as collaborators of the enemy cells: under the electron microscope and using other special microscopic techniques, he discovered that the nerve cells are in close contact with the tumour cells and form cell-cell contacts, so-called synapses. In this way, they transmit excitation signals to the long cell extensions of the glioblastoma cells. This is a driving force for tumor growth and the tumor cells to swarm into the brain tissue. "We currently assume that brain activity supports the glioblastomas in their spread," says Varun Venkataramani.
The researchers carried out their investigations on tumors from human glioblastoma cells that they had transferred to mice, cell cultures with human nerve and tumor cells as well as tissue samples from patients. Among other things, they used a wide range of modern microscopy techniques to visualize the micrometer-sized synapses and the signal transmission to the tumour cells. "Only with such a wide range of methods were we able to show that the cell-cell contacts on the nerve cell side are actually normal excitatory synapses that function in exactly the same way and can also be inhibited with the same substances," says Thomas Kuner. "This opened the door to clinical application."
In animal experiments, the transmission of excitation signals from nerve to tumor cells could be interrupted with a drug that is used in epilepsy. In mice that received this drug, the glioblastoma grew much more slowly. "We didn't stop at this point, but worked quickly to get a clinical trial underway. Since January 2024, the first patients with recurrent glioblastoma receive the epilepsy drug before surgery as part of this study," says Frank Winkler, hoping that the results from 2019 may soon be able to support the treatment. Up to 66 patients across Germany will take part in the study conducted by the UKHD and the National Center for Tumor Diseases (NCT) Heidelberg.
There is now increasing scientific evidence that the nervous system could also play a central role in other types of cancer. For the scientists Venkataramani, Winkler and Kuner, the award-winning work therefore marks the cornerstone of a new field of research, "Cancer Neuroscience", which aims to explore the complex interplay between the nervous system and cancer. "Cancer neuroscience will become increasingly important in cancer research in the future. We will play our part, for example, in the collaborative research center (Sonderforschungsbereich) "UNITE GLIOBLASTOMA - Overcoming the resistance of glioblastomas to therapy (SFB1389)" and in other planned research networks," says Frank Winkler. The collaborative research center (Sonderforschungsbereich) "UNITE GLIOBLASTOMA is coordinated from Heidelberg, speaker is Wolfgang Wick, Heidelberg Medical Faculty of Heidelberg University, Medical Director of the Department of Neurology at Heidelberg University Hospital (UKHD) and Head of the Clinical Cooperation Unit "Neurooncology" of the UKHD and the German Cancer Research Center (DKFZ).
Literature
Venkataramani V, Tanev DI, Strahle C, et al. Glutamatergic synaptic input to glioma cells drives brain tumour progression. Nature. 2019;573(7775):532-538. doi:10.1038/s41586-019-1564-x
Further Information
BIAL Award in Biomedicine 2023 - Award Ceremony - YouTube
Contact
Prof. Dr. med. Thomas Kuner
Director
Department of Functional Neuroanatomy
Institute of Anatomy and Cell Biology
E-mail: thomas.kuner@uni-heidelberg.de
Prof. Dr. med. Frank Winkler
Managing Senior Physician
Neurological University Hospital Heidelberg
Clinical Cooperation Unit Neurooncology, German Cancer Research Center
E-mail: frank.winkler@med.uni-heidelberg.de
Dr. med. Dr. rer. nat. Varun Venkataramani
Head of research group
Neurological University Hospital Heidelberg
Department of Functional Neuroanatomy
Institute of Anatomy and Cell Biology
Clinical Cooperation Unit Neurooncology, German Cancer Research Center
E-mail: varun.venkataramani@med.uni-heidelberg.de