Newly discovered signalling pathways important for future brain cancer therapy

2019-08-21

Each year, more than 1 300 people in Sweden are diagnosed with brain cancer. An international collaboration with researchers from the University of Wales, the United States and IGP have now uncovered molecular targets that might lead to a new generation of brain cancer therapies. The results are published today in a paper in the journal Cancer Discovery.

Glioblastoma is a lethal form of brain tumour with a poor prognosis as they are resistant to therapy and infiltrate structures in the healthy brain.

“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 tumour growth and are responsible for the spread of the cancer around the body. If we can understand the activities of cancer stem cells we can target these particular cells, which we believe will enable us to develop a more effective therapy,” says Florian Siebzehnrubl at Cardiff University, who has led the study.

The researchers wanted to determine which signals allow cancer stem cells in the brain continue to give rise to new cancer cells and why they are resistant to current cancer therapies. The identified molecules, called ADAMDEC1 and FGFR1, are proteins that are given off from cancer stem cells to communicate with other cells around them. The proteins help keep the cancer stem cells healthy so that they can continue to divide and grow the tumour.

“When we blocked the genes for ADAMDEC1 and FGFR1, or by inhibiting the activity of the two proteins, we found that the glioblastoma stem cells were killed off and the tumour growth slowed down. This makes these proteins possible therapeutic targets for glioblastoma, and through further research we can investigate their effectiveness as therapeutic targets,” says Florian Siebzehnrubl.

The results indicate new signalling pathways for the regulation of cancer stem cells, by which this cell population can selectively access key nutrients in their surrounding environment. It is also an example of how cancer stem cells can engage in communication with their microenvironment to ensure their growth.

Glioblastoma is a disease that differs widely between different patients, which makes it very difficult to treat. Researchers in Uppsala have established a biobank of cells from glioblastoma patients, that has been used it this project. The new study has laid the foundations to 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 studies of biobanks material with cultured cells from many patients. This can allow us to uncover new mechanisms of cancer vulnerabilities that may be turned into personalised therapies,” says Karin Forsberg Nilsson at IGP, who has participated in the study from Uppsala University.

More information:
Paper in Cancer Discovery
Karin Forsberg Nilsson’s research