Different Cardiotoxicity of Palbociclib and Ribociclib in Breast Cancer: Gene Expression and Pharmacological Data Analyses, Biological Basis, and Therapeutic Implications.

Breast cancer is the most frequent tumor in women. The recent advent of cyclin-dependent kinase (CDK) 4/6 inhibitors palbociclib and ribociclib has represented a major step forward for patients with hormone receptor-positive breast cancer. These two agents have showed similar efficacy in terms of breast cancer outcome but different cardiotoxic effects. In particular, ribociclib, but not palbociclib, has been associated with QT interval prolongation, and the mechanisms underlying this event are still unclear. In order to clarify such difference, we matched the candidate genes associated with QT interval prolongation with genes whose expression is altered following palbociclib or ribociclib treatment. We also investigated whether pharmacokinetic and pharmacodynamic characteristics, such as IC