Scientists 'reverse engineer' brain cancer cells to find new targets for treatment

23 April 2019

Glioblastoma is one of the most devastating types of cancer, with few existing treatment options. It is a leading cause of cancer-related death in both children and young adults. Scientists have 'reverse engineered' brain cancer stem cells gene by gene, uncovering multiple potential targets for this hard-to-treat cancer.

The research is a collaboration between the University of Toronto, The Hospital for Sick Children (SickKids), and the University of Calgary. Findings were published in the journal Cell Reports, making this the first published study to systematically profile a large panel of patient-derived brain tumour cells that have stem cell properties.

"We think that, in one big experiment, we have uncovered many new targets for glioblastoma, some of which were surprising," says Dr Peter Dirks, staff neurosurgeon and senior scientist at SickKids, who was involved in the study. “These glioblastoma stem cells are also resistant to treatment, which is one reason that these tumours are so hard to cure. We need new ways to disrupt these cells specifically if we are going to give people a better chance of survival.”

The emergence of the CRISPR-Cas9 technology has provided pa powerful new way to explore cancer biology through genome-wide screens. Dr Stéphane Angers, co-principal investigator of the study and professor at the Leslie Dan Faculty of Pharmacy, University of Toronto, specialises in the use of CRISPR-Cas9 in cancer. Taking 10 unique patient-derived glioblastoma stem cell cultures collected by the Dirks research team, scientists used CRISPR 'cell fitness screens' to determine which genes in the cancer stem cells were required for the cells to survive and to grow, therefore, important for tumour progression.

“Cancer stem cells fuel the growth of tumours and progression of the disease,” says Angers. “If you know which genes are necessary for these cells to survive and proliferate, you can then look at ways to attack or block these genes and stop tumour growth in its tracks.”

By systematically knocking out each of the 20,000 genes, one by one, researchers found multiple genetic vulnerabilities and revealed a wealth of data that can be further mined to identify possible drug targets for glioblastoma. “This is one of the first studies of its kind, where CRISPR screens are performed directly in multiple freshly isolated patient cells in parallel,” says Angers. “This study has provided a massive amount of new information that the research community can now interrogate to help design new treatment strategies.”



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