CRISPR Identifies Cancer Drug Targets
A team from the Wellcome Trust Sanger Institute and Broad Institute have used CRISPR-Cas9 to identify key genes required for cancer survival. Over 18,000 genes from 30 different cancer types were screened, a computational framework then developed to prioritise the 600 most promising drug development targets.
One target, Werner syndrome RecQ helicase (WRN), was present in a number of cancer types with a specific DNA defect, microsatellite instability (MSI). MSI-high tumours occur when “mismatch repair” genes malfunction and the DNA sequence contains abnormal repeated nucleotides. Such tumours need WRN to live, it was discovered. Because of this, the team noted that mutations in the mismatch repair gene alongside inhibition of the WRN-encoding gene could ensure the death of cancer cells.
Francesco Iorio, co-first author of the Wellcome study, said: “To give a new drug the best chance of succeeding in the very final phases of clinical trials, it is crucial to select the best and most promising drug target at the beginning of the drug development process…for the first time, in a data-driven way, we provide guidance at a genome-scale on which new therapeutic targets should be put forward for the development of new anti-cancer drugs.
“The Broad Institute-led researchers suggest that further studies will be needed to understand “the intersecting roles of MMR deficiency and genomic lesions in MSI with WRN dependence.”