Sensitizing Tumor Cells by Targeting Death Receptor Signaling Inhibitors

摘要: Therapies aimed at death receptor signaling using FasL or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as agonists have become an active area of research in the development novel anticancer therapies. Systemic delivery causes hepatotoxicity, limiting its use to local administration (1). In contrast, preclinical studies with TRAIL show that systemic soluble form is well tolerated nonhuman primates (2, 3, 4). Exposure normal human cells was also tolerated, whereas induced apoptosis numerous malignant cell lines were analyzed initial (2,5,6). However, more and fresh explants examined, it became clear fails induce significant many transformed (7, 8, 9, 10, 11). Numerous been undertaken understand mechanisms resistance, strategies enhance sensitivity overcome resistance devised. this chapter role, function, regulation pathway inhibitors, how they can be targeted therapeutically, implications for future cancer therapies will discussed.