We have now tested if selective CDK8/19 inhibitors, Senexin B and SNX631, could prevent the development of Palbociclib resistance in ER-positive breast cancers....when CDK8/19 inhibitors are added together with Palbociclib, resistance does not develop....These results suggest specific mechanisms through which CDK8/19 inhibition prevents the development of adaptive resistance to Palbociclib. These in vitro findings are currently being investigated in vivo in an ER-positive breast cancer xenograft model.