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CRISPR reveals new cancer drug targets

11 May 2015
Appeared in BioNews 802

Molecular biologists have used gene-editing technology to identify promising targets for anti-cancer drugs. 

The researchers say the new method - which uses the CRISPR/Cas 9 gene-editing technique - could allow scientists to rapidly create a 'master catalogue' of the best drug targets for each type of cancer.  

Dr Christopher Vakoc and his team at Cold Spring Harbor Laboratory in New York adopted a fresh approach to cancer drug development by seeking out only those parts of a gene that encode a protein's 'binding pockets'. These pockets sit on the surface of a protein and, when a drug molecule is the right size and shape to fit inside a pocket, it can stop it from functioning.  

Using acute myeloid leukaemia cells, they used the CRISPR/Cas 9 gene-editing technique to cut out the precise sections of DNA that are responsible for each protein's binding pockets. In doing so, they were able to mimic the effect of a drug binding to that pocket - if cutting out that section of protein stopped the cancer cells from growing, then it might be a potential target for an anti-cancer drug. 

Dr Vakoc and his team used this approach to identify 25 protein domains that are essential for the survival of acute myeloid leukaemia cells - six that are already under investigation for drug development, plus 19 new potential targets. They published their results in Nature Biotechnology.  

'We can now take a very complicated protein and scan across it and try to visualise which surfaces matter most for that protein to work. We can draw a bulls-eye around the domains critical for a certain disease,' said Dr Vakoc.  

The researchers examined five proteins expressed in these leukaemia cells, but chose not to examine every single section of each protein. 'For entirely pragmatic reasons, our lab is prioritising our search to the kinds of targets [that] chemists like and are willing to design drugs against,' explained Dr Vakoc. 'We want to have an impact on cancers in the near term.' 

The researchers suggest that this approach could be used to rapidly identify all the key drug targets for each type of cancer cell. 'We now feel like we have the technology to see every weakness that a cancer cell possesses along its cell proteins. It collapses the druggable genome,' Dr Vakoc told GenomeWeb.

SOURCES & REFERENCES
CRISPR Dips into Cancer’s Pockets of Vulnerability
Genetic Engineering & Biotechnology News |  12 May 2015
CRISPR Screens Suggest Protein Domains Essential to Cancers, Novel Targets for Therapy
GenomeWeb |  12 May 2015
Discovery of cancer drug targets by CRISPR-Cas9 screening of protein domains
Nature Biotechnology |  11 May 2015
Targeting Protein Domains with CRISPR
The Scientist |  13 May 2015
Using CRISPR, biologists find a way to comprehensively identify anti-cancer drug targets
Eurekalert (press release) |  11 May 2015
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