Project Description
New response biomarkers for the MEK inhibitor cobimetinib
Correlating drug response to gene expression
Cobimetinib is a small molecule inhibitor of the MEK kinase that has been approved for use in advanced melanoma since 2015.
The current approval is for combination treatment, awaiting further proof of the efficacy of MEK inhibitors as single agents in genetically well-defined patient populations.
We tested cobimetinib in the 102 cell lines of the Oncolines™ cell panel and correlated the response profile with the basal expression of 383 clinically actionable genes for each cell line.
Significant correlations were cross-validated by comparison with responses of other MEK inhibitors in Oncolines™ and pharmacogenomic databases, thereby reducing the number of false positive correlations.
The best validated gene expression biomarker for cobimetinib is high expression of the ETS-transcription factors ETV4 and ETV5, indicating that cancers with high expression of these genes could be particularly responsive to cobimetinib.