The clinical success rate of new oncology drugs is only 3.4% compared to 20.9% in other disease types (Wong et al, 2018). One contributing factor to this issue is the testing systems used, with two-dimensional (2D) monolayer assay formats as the traditional mainstay of high throughput screening. Although 2D monolayer assays have identified many successful drugs, it is increasingly recognized that they do not accurately model key aspects of the three-dimensional (3D) tumor environment. Therefore, the adoption of high throughput screening approaches using 3D assays to complement 2D approaches could substantially improve prediction of clinical outcomes and reduce the high failure rate of cancer drugs in clinical trials.
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A major study has been undertaken to gain a better understanding of thousands of mutations in the BRCA1 gene - a key gene in breast and ovarian cancers.
A revolution is under way in functional genomics which is spearheaded by the CRISPR-Cas9 system and its application to pooled genetic screening. Remarkable new tools, made possible by dCas9, are coming to fruition that will allow for a new kind of interrogation of gene function, allowing us to ask more sophisticated questions about the biology of drug targets.
This blog explores how a selection of HAP1 knockout cell lines were used to confirm the involvement of DDR pathways in compounds mode of action, demonstrating opportunities for the exploitation of synthetic lethal interactions.
Review of a paper published in Nature .com, detailing analysis of CRISPR-Cas9 sensitivity (Drop-out) screening, which resulted in the development of a streamlined screening pipeline to evaluate fundamental aspects of functional genomic screening.
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.