Recent studies showed that pharmacological inhibition of CDK4/6 led to a rapid, TSC2-dependent reduction of mTORC1 activity in multiple cell lines including the breast cancer cell line MCF7 [40], whereas genetic depletion of TSC2 in MCF7 cells resulted in sustained mTORC1 activity during palbociclib treatment and evoked a complete senescence response [41]. The gene discussed is TSC2; the disease is breast cancer.