ArticleCancer biology & therapy2014
DR4 specific TRAIL variants are more efficacious than wild-type TRAIL in pancreatic cancer.
Article in Cancer biology & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 30 citations in OpenAlex.
- Turn TRAIL Into Better Anticancer Therapeutic Through TRAIL Fusion Proteins.Cancer medicine · 2025Review
- Recent Advances in the Development of Nanodelivery Systems Targeting the TRAIL Death Receptor Pathway.Pharmaceutics · 2023Review
- Receptor Specificity Engineering of TNF Superfamily Ligands.Pharmaceutics · 2022Review
- Review
- Genetically Modified DR5-Specific TRAIL Variant DR5-B Revealed Dual Antitumor and Protumoral Effect in Colon Cancer Xenografts and an Improved Pharmacokinetic Profile.Translational oncology · 2020Article
- Accelerated degradation of cFLIPScientific reports · 2019Article
- Apoptosis and apoptotic body: disease message and therapeutic target potentials.Bioscience reports · 2019Review
- Review
- Cancer preventive effect of recombinant TRAIL by ablation of oncogenic inflammation in colitis-associated cancer rather than anticancer effect.Oncotarget · 2018Article
- LPS promotes resistance to TRAIL-induced apoptosis in pancreatic cancer.Infectious agents and cancer · 2017Article
- Therapeutic applications of TRAIL receptor agonists in cancer and beyond.Pharmacology & therapeutics · 2015Review
- The structure of the death receptor 4-TNF-related apoptosis-inducing ligand (DR4-TRAIL) complex.Acta crystallographica. Section F, Structural biology communications · 2015Article
- TRAIL-receptor preferences in pancreatic cancer cells revisited: Both TRAIL-R1 and TRAIL-R2 have a licence to kill.BMC cancer · 2015Article
- Mining for Candidate Genes Related to Pancreatic Cancer Using Protein-Protein Interactions and a Shortest Path Approach.BioMed research international · 2015Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Current treatment modalities for pancreatic carcinoma afford only modest survival benefits. TRAIL, as a potent and specific inducer of apoptosis in cancer cells, would be a promising new treatment option. However, since not all pancreatic cancer cells respond to TRAIL, further improvements and optimizations are still needed. One strategy to improve the effectiveness of TRAIL-based therapies is to specifically target one of the 2 cell death inducing TRAIL-receptors, TRAIL-R1 or TRAIL-R2 to overcome resistance. To this end, we designed constructs expressing soluble TRAIL (sTRAIL) variants that were rendered specific for either TRAIL-R1 or TRAIL-R2 by amino acid changes in the TRAIL ectodomain. When we expressed these constructs, including wild-type sTRAIL (sTRAIL(wt)), TRAIL-R1 (sTRAIL(DR4)) and TRAIL-R2 (sTRAIL(DR5)) specific variants, in 293 producer cells we found all to be readily expressed and secreted into the supernatant. These supernatants were subsequently transferred onto target cancer cells and apoptosis measured. We found that the TRAIL-R1 specific variant had higher apoptosis-inducing activity in human pancreatic carcinoma Colo357 cells as well as PancTu1 cells that were additionally sensitized by targeting of XIAP. Finally, we tested TRAIL-R1 specific recombinant TRAIL protein (rTRAIL(DR4)) on Colo357 xenografts in nude mice and found them to be more efficacious than rTRAIL(wt). Our results demonstrate the benefits of synthetic biological approaches and show that TRAIL-R1 specific variants can potentially enhance the therapeutic efficacy of TRAIL-based therapies in pancreatic cancer, suggesting that they can possibly become part of individualized and tumor specific combination treatments in the future.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.