CAF-derived factors such as TGF-β and PDGF activate SMAD, PI3K/AKT and MAPK signaling, leading to upregulation of anti−apoptotic proteins (e.g., Bcl-2, Survivin) and enhanced resistance to 5-fluorouracil and oxaliplatin in colorectal cancer (83–86). Here, BCL2 is linked to colorectal cancer.