In an international study with SciLifeLab affiliated researchers from Uppsala and Stockholm University, changes in glioblastoma cells were mapped and compared with 1544 different drugs to predict responses of individual cell cultures to several existing drug classes. The new biobank may be used to repurpose drugs and discover new treatments. The results are published in the journal Cell Reports.
Glioblastoma (GBM) is a form of cancer with a very poor prognosis that affects the brain. Today we know that glioblastoma tumors contain many genetic changes that vary between patients. Despite this, there are still no good methods for tailoring treatments based on these differences, and most patients still receive similar treatments.
“It was against this background that we investigated how glioblastoma cells from 100 Uppsala patients responded to different drugs. To do this, we used cell cultures, which were grown from patient samples, and tested more than 1,500 drug substances to see how the cells responded”, says senior author Sven Nelander (SciLifeLab/Uppsala University) in a press release from Uppsala University.
The large-scale measurements of drug responses were carried out at the Science for Life Laboratory Drug Discovery and Development platform (DDD). Genomic profiling of the GBM cell cultures was conducted at the Science for Life Laboratory core units and the Uppsala Academic Hospital Array and Analysis unit.
The researchers then used an algorithm to investigate which changes in the cancer cells that could best predict the effect of an individual drug. In mapping these changes, they were able to group the tumors into two main subgroups based on drug response and mutations in certain genes.
“By classifying the cells in several different ways, we discovered unexpected connections between important genes, signaling pathways in the cells and different drugs. This in turn led to us finding new opportunities to combine different drugs for maximum effect. Our results can be used as a starting point for further research aimed at increasing the precision and adapting the treatment of glioblastoma for different patients. They can also be used to find new areas of use for already known drugs”, says Sven Nelander in the press release.
The study was funded by, among others, the Cancer Foundation, AstraZeneca and the Swedish Research Council and is a collaboration between researchers in Uppsala, London, Singapore and the USA.
Photo: Mikael Wallerstedt