Treatment options for patients with esophageal squamous cell carcinoma (ESCC) often result in poor prognosis and declining health-related quality of life. Screening FDA-approved drugs for cancer chemoprevention is a promising and cost-efficient strategy. Here, we found that dronedarone, an antiarrhythmic drug, could inhibit the proliferation of ESCC cells. Moreover, we conducted phosphorylomics analysis to investigate the mechanism of dronedarone-treated ESCC cells. Through computational docking models and pull-down assays, we demonstrated that dronedarone could directly bind to CDK4 and CDK6 kinases. We also proved that dronedarone effectively inhibited ESCC proliferation by targeting CDK4/CDK6 and blocking the G0/G1 phase through RB1 phosphorylation inhibition by in vitro kinase assays and cell cycle assays. Subsequently, we found that knocking out CDK4 and CDK6 decreased the susceptibility of ESCC cells to dronedarone. Furthermore, dronedarone suppressed the growth of ESCC in patient-derived tumor xenograft models in vivo. Thus, our study demonstrated that dronedarone could be repurposed as a CDK4/6 inhibitor for ESCC chemoprevention.

The first ever investigation into the impact of the Covid pandemic on children and young people with brain tumours has revealed how investigations or treatments were frequently postponed as key people or resources were not available.The “heartbreaking” impact is revealed in a study in the British Medical Journal Open led by Lancaster University and Cambridge University Hospitals NHS Foundation Trust. One caregiver said: ”When [daughter] came out of theatre, I wasn't allowed to go and see her, because I wasn't the designated parent. And it is heartbreaking, absolutely heartbreaking, to not be able to go and see that your child is okay.”