Important knowledge on drug response from brain tumour samples
In a recent paper in the journal Science Translational Medicine, IGP researcher Verónica Rendo together with American colleagues confirm the vital role of tumour tissue samples for studying how cancer drug compounds enter the tumour and how they kill the tumour cells. This is important knowledge for developing new cancer therapies.
Microscope image of brain tissue where the amount of navtemadlin is indicated in different colours (middle). To the left (in pink) and to the right (in red) the amounts of control substances are indicated.
In clinical trials of new drugs, researchers study for instance the effect of the drug on the disease. However, in the field of neuro-oncology, when a drug is tested and the trial fails, it is often not possible to determine why. A reason for this is the limited availability of biopsy samples collected over the course of a patient’s treatment history. This impairs the possibilities to study how the drug enters the brain and its effect on the cancer cells.
In a study from Harvard, USA, where IGP researcher Verónica Rendo is first author, the researchers performed a window of opportunity study of the drug compound navtemadlin. This was done by treating brain tumour patients with the substance before they were operated for a recurrent tumour. Subsequently, the researchers also had access to the tumour tissue removed during the surgery.
“This way we could compare the patients’ biopsies taken at diagnosis, i.e. before treatment with navtemadlin, with samples taken during surgery. We were able to confirm that the compound crosses the blood brain barrier and enters the tumour. We also found the doses we used were sufficient to affect the tumour cells,” says Verónica Rendo.
The researchers also saw that navtemadlin had its intended effect on the brain tumour cells, in this case activating a signalling pathway that leads to cell death. By analyzing the biopsies, they also discovered that patients relapse by different mechanisms than observed in other cancer types.
“In summary, our study highlights the importance of studying tissue samples during clinical trials to determine the effect of a drug and how the cancer cells are affected. Our findings also suggest that the effect of navtemadlin could be enhanced by combining it with another brain tumour drug, that has a different mechanism of action, says Verónica Rendo.