www.frontiersin.org/articles/10.3389/fmolb.2021.628332/full
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trigger extrinsic apoptotic pathway in malignant cells
p53 independent manner
agonistic properties due to their intracellular death domain (DD) which transmits the apoptotic signal.
membrane-bound TRAIL (mTRAIL)
soluble TRAIL (sTRAIL)
caspase–8 which directly enables the activation of other effector caspases, including the executor caspases, caspase-3 and caspase-7 triggering the final steps of apoptosis
engage the intrinsic (mitochondrial) apoptotic pathway
chimeric antigen receptor (CAR) T cell cytotoxicity
TRAIL to promote pro-tumorigenic activity against tumor cells regardless of their p53 status is thought to be the major advantage of TRAIL-based therapies
KRAS-mutated cancers where TRAIL signaling was newly found to mediate migration, invasion, and metastasis.
TRAILshort
extracellular vesicles and serves as a dominant negative ligand for DR4 and DR5
induce also the antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytolysis (CDC)
ability to trigger apoptosis in the absence of TRAIL-R2 crosslinking
advanced NSCLC patients, tigatuzumab did not improve the efficacy of carboplatin/paclitaxel
rapid clearance from the serum
phase II in patients with NSCLC and B-cell lymphomas
improved PFS (6.4 months vs. 3.5 months in the placebo arm)
circularly permuted TRAIL, also known as CPT
CPT-mediated liver injury
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