Project Description

Biomarker discovery for CDK4/6 inhibitors

  • 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.

Link to the publication describing these findings (Uitdehaag et al, 2019)