Multiomics Profiling Establishes the Polypharmacology of FDA-Approved CDK4/6 Inhibitors and the Potential for Differential Clinical Activity.

We compared three CDK4/6 inhibitors that have recently emerged as highly promising agents for advanced breast cancers by performing transcriptional profiling (mRNA-Seq) on a panel of seven breast cancer cell lines following 6 or 24 hours of drug exposure at concentrations ranging from 0.3 to 3.0 uM. Overall design: mRNA levels for 7 breast cancer cell lines treated with one of three CDK4/6 inhibitors (abemaciclib, palbociclib, or ribociclib) at either 0.3 uM, 1.0 uM (only for MCF7), or 3.0 uM for either 6 or 24 hours.