RB1 and osteosarcoma: Conversely, long-term treatment of pancreatic cancer cells with palbociclib actually resulted in upregulation of mTOR signaling [44], and Rb loss or CDK4/ 6 inhibition activated mTORC2 and Akt in ovarian cancer, TNBC, and osteosarcoma cells [45], suggesting that the impact of CDK4/6 on mTOR signaling may vary by tumor type or genetic background.