Thursday, December 5, 2013
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Assays & screens
In vitro screening for genetic signatures associated with
sensitivity to targeted cancer therapeutics
Combined genetic and
chemical screening of lung cancer cells for altered genetic signatures could
reveal sensitivity to therapeutic candidates. The screening approach involved
identifying small molecule inhibitors and small interfering RNAs that reduced
growth of cancer cells from a patient tumor sample but had no effect on
growth of normal cells from the same patient. The small molecules and siRNAs
were then tested in a panel of 91 non-small cell lung cancer (NSCLC) cell
lines to identify common signatures of sensitivity. K-Ras (KRAS) and serine/threonine kinase 11
(STK11; LKB1) mutations
correlated with sensitivity to knockdown of constitutive photomorphogenic 1
(COP1; RFWD2). In addition, a
seven-gene expression signature correlated with sensitivity to an indolotriazine-based
compound. Next steps could include using this approach to identify
sensitivity to therapeutics in additional cancer types.
Published online Dec. 5, 2013
Patent and licensing status
Kim, H.S. et al. Cell;
published online Oct. 24, 2013;
Contact: Michael A. White, The University of Texas
Southwestern Medical Center, Dallas, Texas
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