In patients with advanced ER+ breast cancer receiving daily oral doses of 125 mg palbociclib, the mean plasma concentration of palbociclib at steady-state is 116 ng/mL (259 nmol/L; ref. 26), indicating that CDK9 inhibitor synergy in palbociclib-resistant cells is achieved at, or near, clinically relevant concentrations of palbociclib, and could translate into using subtherapeutic combination dosing to avoid toxicities. Here, CDK9 is linked to breast cancer.