Massive Amount of Possible New Target Information Generated in Gene-by-Gene, Genome-Wide CRISPR-Cas9 Screen of Patient-Derived Glioblastoma Cancer Stem Cells; One Existing, Potentially Helpful Small Molecule Drug Identified

Glioblastoma is one of the most devastating forms of cancer, with few existing treatment options. It is also a leading cause of cancer-related death in 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. This work is a collaboration among the University of Toronto, The Hospital for Sick Children (SickKids), and the University of Calgary. Findings were published online on April 16, 2019 in Cell Reports, making this the first published study to systematically profile a large panel of patient-derived brain tumor cells that have stem cell properties. The open-access article is titled “Genome-Wide CRISPR-Cas9 Screens Expose Genetic Vulnerabilities and Mechanisms of Temozolomide Sensitivity in Glioblastoma Stem Cells.” "We think that, in one big experiment, we have uncovered many new targets for glioblastoma, some of which were surprising," says Peter Dirks (photo), MD, PhD, co-principal investigator of the study, Staff Neurosurgeon and Senior Scientist at SickKids. "These glioblastoma stem cells are also resistant to treatment, which is one reason that these tumors 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 research team also found that adult glioblastoma cells are actually dependent on the same genes that are important for brain development in infancy and early childhood. "This really emphasizes how much research needs to be done to understand the developing human brain," says Dr. Dirks, who, in 2003, was the first to discover the existence of cancer stem cells in brain tumors.
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