License to kill tumors: how much hope is justified for trail?
In 1995, a new cytokine termed TRAIL (tumor necrosis factor--related apoptosis-inducing ligand) was discovered and demonstrated to selectively induce programmed cell death in transformed cell lines. Preclinical cytotoxicity studies in mice and nonhuman primates have produced promising results by demonstrating that TRAIL exerts potent tumoricidal activity but lacks severe toxicity towards normal tissues making it a potentially ideal candidate for cancer therapy. This article reviews aspects of our current understanding of TRAIL signaling pathways and summarizes how this knowledge is currently being translated into TRAIL-based tumor-selective therapeutic strategies.
Frank
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Biochemistry Section, Surgical Neurology Branch, NINDS, NIH, Bethesda 20892, USA. frankst@ninds.nih.gov
Ebert
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D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D006801:Humans; D008562:Membrane Glycoproteins / Q000494:pharmacology* / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha