publication date: Jul. 10, 2020

Clinical Roundup

Drug screens and CRISPR combine to make better cancer drugs, collaboration of researchers say

Scientists at the Wellcome Sanger Institute, EMBL’s European Bioinformatics Institute and AstraZeneca combined drug response data with CRISPR genetic screens across hundreds of cancer cell lines to better understand how drugs target cancer cells.

The research, published in Molecular Systems Biology, identified the mechanism-of-action in half of the 397 drugs tested. This improved understanding of the biological mechanisms underpinning drug response helps researchers better develop cancer drugs.

Historically, the success rate of drug development has been low, with fewer than 10% of prospective compounds proceeding to clinical trials.

Cancer Dependency Map have created reference collections of cancer cell models from patient tumours that can be grown in the laboratory and used widely in research. One use of these cell models is for pharmacological screens, which test the activity of anticancer drugs to identify how sensitive particular cancers are to particular compounds.

Another breakthrough has been the development of CRISPR-Cas9 technology to edit the genes in cancer cells lines, turning them off one-by-one to measure how critical they are for the cancer to survive.

In this new study, researchers for the first time combined CRISPR-Cas9 screens with pharmacological screens for 397 unique anti-cancer compounds across 484 cancer cell lines. Compounds included FDA-approved cancer drugs, drugs in clinical development, and compounds in early development.

The team investigated the extent to which drug sensitivity corresponded to CRISPR knock-out of drug targets by searching for associations between the two datasets across the 484 cell lines. They identified 865 significant associations between drug response and gene dependency.

“When a molecular pathway or function is … Continue reading Drug screens and CRISPR combine to make better cancer drugs, collaboration of researchers say

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Copyright (c) 2020 The Cancer Letter Inc.