title: Targeting TRAIL in the treatment of cancer: new developments.
abstract: BACKGROUND
  While apoptosis is critical for maintaining homeostasis in normal cells, defective apoptosis contributes to the survival of cancer cells. TNF-related apoptosis-inducing ligand (TRAIL)-targeted therapy has attracted significant effort for treating cancer, but the clinical results have revealed limitations. The authors review the current status of development of TRAIL-targeted therapy with an outlook towards the future.
  
  
  METHODS
  Recombinant human proteins, small molecules and agonistic monoclonal antibodies targeting death receptors that trigger TRAIL-mediated apoptosis are covered in this article. The authors review both intrinsic and extrinsic apoptotic pathways, highlighting how the apoptosis serves as a promising therapeutic target. They also review different categories of TRAIL pathway targeting agents and provide a brief overview of clinical trials using these agents. The authors discuss the limitations of conventional approaches for targeting the TRAIL pathway as well as future directions.
  
  
  CONCLUSIONS
  The development of better combination partners for pro-apoptotic TRAIL pathway modulators including novel agents inhibiting anti-apoptotic molecules or targeting alternative resistance pathways may improve the chances for anti-tumor responses in the clinic. Developing predictive biomarkers via circulating tumor cells/DNA, apoptosis signal products, and genetic signatures/protein biomarkers from tumor tissue are also suggested as future directions.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Department of Cancer Medicine, Breast Medical Oncology , Houston, TX 77030 , USA.
authors.forename: Bora
authors.initials: B
authors.lastname: Lim
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Allen
authors.forename: Varun V
authors.initials: VV
authors.lastname: Prabhu
authors.forename: Mala K
authors.initials: MK
authors.lastname: Talekar
authors.forename: Niklas K
authors.initials: NK
authors.lastname: Finnberg
authors.forename: Wafik S
authors.initials: WS
authors.lastname: El-Deiry
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D011994:Recombinant Proteins
keywords: TRAIL; apo2L; apoptosis; cancer therapy; extrinsic pathway; intrinsic pathway; novel therapeutics; targeting apoptosis pathway