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TRAIL: A Sword for Killing Tumors

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

Document Type: Research Article

DOI: https://doi.org/10.2174/092986710793176285

Publication date: 2010-10-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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