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Cancer genomics

Constructing a 'cancerpaedia'

Nature Reviews Drug Discovery volume 11, page 353 (2012)Cite this article

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The two groups of researchers each assembled a panel of hundreds of cancer cell lines and characterized multiple genomic features, gene expression and copy number variation. Each group then conducted a screen with anticancer drugs and used various bioinformatic analyses to correlate drug activity with changes in one or more genes: Barretina et al. profiled 24 drugs in 479 cell lines, and Garnett et al. profiled 130 drugs on 275–507 lines. The results showed a number of known interactions between gene mutations and drug sensitivities — such as changes in BRAF associated with RAF inhibitors — but several previously unseen connections emerged immediately.

For example, Barretina et al. showed that mutations in NRAS in some cell lines lead to sensitivity to MEK-inhibiting drugs through elevating expression of the aryl hydrocarbon receptor (AHR)gene. These findings could potentially be applied to the clinic by using expression levels of AHR as a biomarker for use of MEK inhibitors instead of NRAS mutations.

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References

ORIGINAL RESEARCH PAPERS

  1. Barretina, J. et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483, 603–607 (2012)

    Article  CAS  Google Scholar 

  2. Garnett, M. J. et al. Systematic identification of genomic markers of drug sensitivity in cancer cells. Nature 483, 570–575 (2012)

    Article  CAS  Google Scholar 

FURTHER INFORMATION

  1. Genomics of Drug Sensitivity in Cancer project: http://www.cancerRxgene.org; Cancer Cell Line Encyclopedia: http://www.broadinstitute.org/ccle/home

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  1. HudsonAlpha Institute for Biotechnology,

    Chris Gunter

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  1. Chris Gunter
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Gunter, C. Constructing a 'cancerpaedia'. Nat Rev Drug Discov 11, 353 (2012). https://doi.org/10.1038/nrd3730

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