TRAIL as a target in anti-cancer therapy.
The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that can initiate apoptosis through the activation of their death receptors. The ability of TRAIL to selectively induce apoptosis of transformed or tumor cells but not normal cells promotes the development of TRAIL-based cancer therapy. Accumulating preclinical studies demonstrate that the TRAIL ligand can effectively induce cancer cell apoptosis. Completed and ongoing Phases I and II clinical trials using TRAIL are showing clinically promising outcomes without significant toxicity. Importantly, TRAIL, DR4 and DR5 can all be induced by chemotherapeutics and/or radiation, which can sensitize cancer cells to TRAIL. Thus, understanding the regulation of the TRAIL apoptosis pathway can help develop more selective TRAIL-based agents for the treatment of human cancer.
Wu
Gen Sheng
GS
Karmanos Cancer Institute, Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA. wug@karmanos.org
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D016896:Treatment Outcome; D015854:Up-Regulation
D000970:Antineoplastic Agents; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human