Biomarker discovery for CDK4/6 inhibitors
Analysis of drug response in relation to gene alterations
- Since 2017, the new therapeutic class of CDK4/6 inhibitors has been approved for use in breast cancer.
- Compounds that belong to this class are e.g. palbociclib, abemaciclib and ribociclib.
- Prior to approval, much effort was invested in identifying patient populations that would give the best response to CDK4/6 inhibitors.
- The markers CDKN2A and RB1 were deemed of sufficient significance to be evaluated in the clinical Phase III trial of palbociclib (PALOMA-2).
- We tested all three CDK4/6 inhibitors, including palbociclib, on the 102 cell lines of the Oncolines™ cancer cell line panel.
By combining genetic information with IC50 data, we conclude that cell lines with CDKN2A(p16INK4A) loss are significantly more sensitive, and that cell lines with RB1 mutations are relatively resistant.
In addition to CDKN2A and RB1, Oncolines™ analysis identified other response biomarkers that might be useful to find new applications for CDK4/6 inhibitors.