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Genes essential to human life – and cancer – identified

30 November 2015
Appeared in BioNews 830

Scientists have used genome-editing technology to identify a core set of 1580 genes that are essential to human life.

The researchers also used the same approach, involving CRISPR/Cas9, to find out which genes are essential to different types of cancer.

'With this CRISPR technology, we can now systematically go through all our biological models for cancer and map out all the tricks cancer cells have to evade drug responses,' lead researcher Professor Jason Moffat of the University of Toronto told Motherboard. 'If we can figure out what to target for every one of those cancers, we can actually build a war chest of therapeutic drugs to target all these different tricks that cancer cells use to grow and divide.'

Using CRISPR/Cas9, which allows genes to be switched on and off quickly and easily, researchers from the University of Toronto analysed the entire human genome. Out of nearly 20,000 genes they identified 1580 core 'fitness genes' which are used by most cellular processes.

The researchers also turned off genes in five different cancer cell lines, including brain, retinal, ovarian and colorectal cancer. They found that each set of cells relied on a different, unique set of fitness genes. Understanding these differences may help to identify drugs that switch off cancer genes without damaging healthy tissue.

Professor Moffat's team were able to successfully predict which drugs would be effective against specific cancer cell lines, based on their mode of action. For example, they found that the diabetes drug metformin acted against a brain cancer cell line, while the antibiotic chloramphenicol was effective against a type of colorectal cancer cell.

Professor David Sabatini, from the Whitehead Institute for Biomedical Research, led another group that recently published similar findings, lending support to the concept.

'My only fear is that we won't find a huge number of genes that differentiate cancer cells and non-cancer cells, and the ones we find won't be druggable,' said Professor Sabatini to The Atlantic. 'But we need the answer. And if those genes are there, we can find them. It'll just take industrialising this approach, with not just tens of cell lines but hundreds.' 

This study has shown the potential of CRISPR for advancing cancer research. 'The Moffat group has developed a powerful CRISPR library that could be used by investigators around the world to identify new  strategies for the treatment of cancer,' said Dr Aaron Schimmer, a medical oncologist at Princess Margaret Cancer Centre in Toronto, who was not involved in the study.

SOURCES & REFERENCES
High-Resolution CRISPR Screens Reveal Fitness Genes and Genotype-Specific Cancer Liabilities
Cell |  25 November 2015
New gene map reveals cancer's Achilles heel
Eurekalert (press release) |  25 November 2015
New Gene Map Shows Cancer's Weak Link
NDTV |  27 November 2015
Now That We Can Edit Cancer's Genes, We Can Make Better Drugs
Motherboard |  25 November 2015
The New Gene-Editing Technique That Reveals Cancer's Weaknesses
The Atlantic |  25 November 2015
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