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.

Boxplot of the correlation of cobimetinib-response and gene expression (genes on y-axis). The more negative the value (x-axis), the better the correlation between high expression and low IC50. The red dots represent cobimetinib, the blue dots are 160 other compounds.
Boxplot of the correlation of cobimetinib-response and gene expression (genes on y-axis). The more negative the value (x-axis), the better the correlation between high expression and low IC50. The red dots represent cobimetinib, the blue dots are 160 other compounds.