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On the Horizon

Leading news, knowledge, and industry trends in genetic research

Screening

15 result(s)

A number of siRNA and shRNA screens have identified targets that exhibit differential dependencies between KRAS mutant and KRAS wild-type tumours, but there is poor overlap between these published studies. Next generation screens that exploit both isogenic cell lines and cancer cell panels, and use a combination of knockdown (si/shRNA) and knock-out (CRISPR-Cas9-sgRNA) methodologies might be more effective at identifying novel targets that withstand validation. However, if we are to detect co-dependence as well as synthetic lethal interactions, screens must be performed under conditions where mutant KRAS alleles are essential for growth.


Ras mutations are amongst the most commonly occurring mutations in human cancer, present in approximately 49% of colorectal and 20% of lung cancers. Of these, mutations in K-Ras G12 and G13 are the most common. Understanding the role of mutant K-Ras in modulating drug response is critical to the successful development of novel therapeutics, and has been hampered by the lack of suitable in vitro tools.


Thanks to next-generation sequencing (NGS), we are starting to understand the mutational changes that occur across the board in the cancer genome. With this knowledge comes potential - novel mutated genes and the proteins that they encode are candidates for prognostic markers and/or new drug targets.


It’s hard to keep up with the rapidly expanding world of CRISPR, and it’s starting to feel like CRISPR screens are being published every week, taking the technique from the cutting edge to the mainstream. If you’d like to understand a bit more about CRISPR screens, here’s a number of fantastic publications that have really moved this technology forward.