The delivery of NO to the PDAC tumor stroma resulted in the reprogramming of activated pancreatic stellate cells, alleviation of tumor desmoplasia, and suppression of antiapoptotic Bcl-2 protein expression, resulting in facilitated tumor penetration by TRAIL and enhanced TRAIL antitumor efficacy in three-dimensional spheroid cultures in vitro and in orthotopic PDAC models in vivo. Here, BCL2 is linked to neoplasm.