New discovery can improve treatment of brain tumours

21 August 2019

Glioblastoma is a lethal form of brain tumour with a poor prognosis, since the tumour is resistant to treatment. In a new study, researchers are trying to understand how glioblastoma stem cells work.

Over 1,300 people are diagnosed with brain cancer in Sweden each year. Now an international collaboration of researchers from Wales, USA and Uppsala have discovered molecular targets that might lead to a new generation of brain cancer therapies.

Glioblastomas are lethal brain tumours with a poor prognosis as they are resistant to therapy and infiltrate the structures of the healthy brain.

However, chemicals that enable brain cancer cells to communicate and grow are a potential target for future therapies, according to new research from the European Cancer Stem Cell Research Institute at Cardiff University, Cleveland Clinic and Uppsala University.

“The aggressive behaviours that we see in glioblastomas can be attributed to cancer stem cells, which are a small population of cells in a tumour that divide to drive the growth of a tumour, and are responsible for the spread of the cancer around the body. If we can understand the activities of cancer stem cells, we can begin to effectively target the cancer stem cells in a tumour, which we believe will enable us to develop a more effective therapy,” says Dr Florian Siebzehnrubl, Cardiff University.

The researchers wanted to investigate the mechanisms that allow cancer stem cells in the brain to keep their cellular properties, which enable them to create new cancer cells and resist current cancer treatments. They identified two biological molecules, called ADAMDEC1 and FGFR1, which play a key role in processes in glioblastoma cancer stem cells, the cells responsible for driving the growth and spread of brain tumours.

 ADAMDEC1 and FGFR1 are proteins given off by cancer stem cells to communicate with other cells around them. These chemicals help to keep the glioblastoma cancer stem cells healthy so that they can continue to divide and grow the tumour.

“By targeting the genes for ADAMDEC1 and FGFR1, or through drugs that specifically interfere with the activity of these two proteins, we see that the glioblastoma stem cells are killed off and the tumour growth slows down. This makes ADAMDEC1 and FGFR1 possible therapeutic targets for glioblastoma, and through further research we can investigate their effectiveness as therapeutic targets,” adds Dr Siebzehnrubl.

“These studies provide a paradigm for cancer stem cell regulation by which this population can selectively access key nutrients embedded within their surrounding microenvironment. Moreover, this is another example through which cancer stem cells can engage in communication with their microenvironment for their growth and preservation,” says Dr. Justin Lathia of Cleveland Clinic Lerner Research Institute.

Karin Forsberg Nilsson, professor at Department
of Immunology, Genetics and Pathology.
Photo: Mikael Wallerstedt

Glioblastoma is a disease that varies widely from patient to patient, which makes it very difficult to treat and understand. Researchers in Uppsala have built up a biobank of cells from glioblastoma patients that have been used in this project. This research has laid a foundation for potentially uncovering a new class of brain cancer therapies, which will hopefully make a difference to the treatment of this lethal disease in the future.

“This project illustrates the importance of combining biobanks with cell culture from many patients, to uncover new mechanisms of cancer vulnerabilities that may be turned into personalised therapies,” adds Professor Karin Forsberg Nilsson of the Department of Immunology, Genetics and Pathology, Uppsala University, who has participated in the study.



Ana Jimenez-Pascual, James S. Hale, Anja Kordowski, Jamie Pugh, Daniel J. Silver
Defne Bayik, Gustavo Roversi, Tyler J. Alban, Shilpa Rao, Rui Chen, Thomas M.
McIntyre, Giorgio Colombo, Giulia Taraboletti, Karl O. Holmberg, Karin Forsberg-
Nilsson, Justin D. Lathia, Florian A. Siebzehnrubl (2019) ADAMDEC1 maintains a growth factor signaling loop in cancer stem cells, Cancer Discovery

Find out more

HGCC – A human glioblastoma cell culture (HGCC) resource

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Last modified: 2022-12-22