Residual brain tumour cells need different treatment from main tumour

15 April 2010

While most of a brain tumour can often be removed surgically, in virtually every case the tumour reappears.

 One reason for this is that sporadic, infiltrative tumour cells will remain in the brain even after most careful surgery. Researchers at the University of Bonn have now subjected these ‘forgotten’ cells to closer scrutiny for the first time.

 While doing this, they were able to show that many of the fundamental properties of these tumour cells were substantially different from the cells in the midst of the tumour mass. The findings could offer an opportunity to explain why radiation or chemotherapy cannot entirely prevent this deadly disease to reoccur.

Patients with a glioblastoma generally undergo surgery as quickly as possible. During the process, starting from the centre of the tumour, the neurosurgeon gently removes diseased tissue until the tumour appears to be removed entirely. Unfortunately, the cancer cells are hard to get hold of. They often migrate far into adjacent, healthy brain tissue. That is why there are basically always some malignant cells remaining after every surgery, from which then new tumours are formed.

The Bonn scientists have now taken a closer look at these residual cells for the first time.

Apart from being provided with samples from the main mass of the tumour for their research, the scientists were also provided with small diagnostic samples from adjacent tissue from 33 patients by the University of Bonn Department of Neurosurgery. 'From the small samples we then extracted and enriched the few tumour cells that would have normally remained in the patient.' Professor Björn Scheffler from the Institute of Reconstructive Neurobiology explains.

Astonishing discovery

While examining these residual cells, the researchers made an astonishing discovery. 'The cancer cells in the vicinity of the tumour have different properties compared to those from the centre of the tumour,' Björn Scheffler's colleague Dr. Martin Glas from the Department of Neurology’s Clinical Neurooncology Unit explains. 'For instance, they are more mobile, they form other receptors, they react differently to radiation therapy or chemotherapeutic substances.'

These findings may offer an intriguing explanation for the yet meagre therapeutic success against the most frequent malignant brain cancer. Although there has been intensive research on this case for more than half a century, a cure is currently not available. On average, glioblastoma patients survive for only about 15 months from the time of initial diagnosis. Although radiation and chemotherapy both are aimed for complete destruction of residual tumour cells after surgery, these weapons apparently remain blunt. There is no other way of explaining that basically every glioblastoma patient will experience a relapse.

The new results could help medicine to upgrade its weapons arsenal against the remaining cancer cells. Up to now, therapies were only tested on the extracted tumour tissue. But even if medication could destroy the actual tumour, this does not have to be true for the malignant residual cells. 'At least, it is worth keeping an eye on this aspect,' Martin Glas and Björn Scheffler say. But at the same time they warn against exaggerated hopes. 'We still have a lot of work to do. For new approaches to therapy we first need to understand the biology of these cells even better.’

This research was funded by the Volkswagen Foundation (Volkswagenstiftung) and the BONFOR Program of the Bonn Faculty of Medicine.


1. Glas M, et al. Residual tumor cells are unique cellular targets in glioblastoma'. Annals of Neurology. Volume 9999 Issue 999A, Published Online: 6 Apr 2010. DOI: 10.1002/ana.22036

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