TRAIL: A Sword for Killing Tumors

S.      Wang

doi:10.2174/092986710793176285

Abstract

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a promising anticancer agent that selectively triggers apoptosis in various cancer cells by interacting with its proapoptotic receptors DR4 and KILLER/DR5. The intensive studies of TRAIL signaling pathways over the past decade have provided clues for understanding the molecular mechanisms of TRAIL-induced apoptosis in carcinogenesis and identified an array of therapeutic responses elicited by TRAIL and its receptor agonists. Preclinical and clinical studies have shown that recombinant TRAIL and the agonistic mono-antibodies targeting TRAIL receptors exhibit potent tumoricidal activities as monotherapies and that the combinatorial therapies of these agents in conjunction with other anticancer modalities such as chemo or radiotherapy amplify the activities of anticancer agents and widen the therapeutic window by overcoming tumor resistance to apoptosis and driving cancer cells to self-destruction. The identification of a number of biomarkers that predict tumor sensitivity of patients to TRAIL-based therapy shed a new light on the personalized therapeutic strategies targeting the TRAIL/TRAIL receptor pathway.

Keywords: Apoptosis, biomarker, cancer therapy, DR4, drug design, KILLER/DR5, TNF receptor superfamily, Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), TRAIL, TRAIL-induced apoptosis, carcinogenesis, chemo or, radiotherapy, Tumor necro-sis factor (TNF)-related apoptosis-inducing ligand (TRAIL), tissue homeostasis, Excessive apoptosis, AIDS, Alzheimer's diseases, Huntington's disease, cardiac ischemia, deficient apoptosis, caspase-dependent pathway, TNF family, anti-TRAIL receptor, TRAIL-sensitive tumors, resistant tumor, homotrimer, DcR1, DcR2, Osteoprotegerin, mDcR1, mDcR2, interferons, TNF, Eu-myc, 5-FU treatment, (FADD), (DED), death inducing signaling complex, Bax, Bak, Bcl-2, nuclear factor-B, mitogen-activated protein kinases, extracellular signal-regulated kinase, JUN N-terminal kinase, (TRADD), c-FLIP, (TRAF2), (RIP), TRAIL apoptotic pathway, XIAP, GALNT14, GALNT3, FUT 6, FUT 3