ArticleMolecular cancer therapeutics2010
A combination of DR5 agonistic monoclonal antibody with gemcitabine targets pancreatic cancer stem cells and results in long-term disease control in human pancreatic cancer model.
Article in Molecular cancer therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 88 citations in OpenAlex.
- Personalizing cancer treatment in the age of global genomic analyses: PALB2 gene mutations and the response to DNA damaging agents in pancreatic cancer.Molecular cancer therapeutics · 2011Trial
- Phosphorylated STYK1 Promotes Gemcitabine Resistance via Autophagy-Mediated Cancer Stemness in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Target FADS1-arachidonic acid-ferroptosis axis: A metabolic bridge linking matrix stiffness to PDAC stemness.Materials today. Bio · 2026Article
- Advances in the study of death receptor 5.Frontiers in pharmacology · 2025Review
- The Microbiome Tumor Axis: How the Microbiome Could Contribute to Clonal Heterogeneity and Disease Outcome in Pancreatic Cancer.Frontiers in oncology · 2021Article
- Molecular Insights Into Therapeutic Potential of Autophagy Modulation by Natural Products for Cancer Stem Cells.Frontiers in cell and developmental biology · 2020Review
- Novel Apoptosis-Inducing Agents for the Treatment of Cancer, a New Arsenal in the Toolbox.Cancers · 2019Review
- Cytoplasmic PARP-1 promotes pancreatic cancer tumorigenesis and resistance.International journal of cancer · 2019Article
- Long non-coding RNAs are emerging targets of phytochemicals for cancer and other chronic diseases.Cellular and molecular life sciences : CMLS · 2019Review
- Assessment of Three-Drug Combination Pharmacodynamic Interactions in Pancreatic Cancer Cells.The AAPS journal · 2018Article
- A missing link between RON expression and oncological outcomes in resected left-sided pancreatic cancer.Oncology letters · 2017Article
- Curcumin sensitizes pancreatic cancer cells to gemcitabine by attenuating PRC2 subunit EZH2, and the lncRNA PVT1 expression.Carcinogenesis · 2017Article
- The long non-coding RNA HOTAIR enhances pancreatic cancer resistance to TNF-related apoptosis-inducing ligand.The Journal of biological chemistry · 2017Article
- Molecular Pathways Controlling Autophagy in Pancreatic Cancer.Frontiers in oncology · 2017Review
- Potential Role of CD133 Expression in the Susceptibility of Human Liver Cancer Stem-Like Cells to TRAIL.Oncology research · 2016Article
- Resistance to Cell Death and Its Modulation in Cancer Stem Cells.Critical reviews in oncogenesis · 2016Review
- Pancreatic cancer stem cells in patient pancreatic xenografts are sensitive to drozitumab, an agonistic antibody against DR5.Journal for immunotherapy of cancer · 2016Article
- Therapeutic applications of TRAIL receptor agonists in cancer and beyond.Pharmacology & therapeutics · 2015Review
- Blockade of autophagy reduces pancreatic cancer stem cell activity and potentiates the tumoricidal effect of gemcitabine.Molecular cancer · 2015Article
- Harnessing the apoptotic programs in cancer stem-like cells.EMBO reports · 2015Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDA) is an aggressive malignancy with one of the worst outcomes among all cancers. PDA often recurs after initial treatment to result in patient death despite the use of chemotherapy or radiation therapy. PDA contains a subset of tumor-initiating cells capable of extensive self-renewal known as cancer stem cells (CSC), which may contribute to therapeutic resistance and metastasis. At present, conventional chemotherapy and radiotherapy are largely ineffective in depleting CSC pool, suggesting the need for novel therapies that specifically target the cancer-sustaining stem cells for tumor eradication and to improve the poor prognosis of PDA patients. In this study, we report that death receptor 5 (DR5) is enriched in pancreatic CSCs compared with the bulk of the tumor cells. Treating a collection of freshly generated patient-derived PDA xenografts with gemcitabine, the first-line chemotherapeutic agent for PDA, is initially effective in reducing tumor size, but largely ineffective in diminishing the CSC populations, and eventually culminated in tumor relapse. However, a combination of tigatuzumab, a fully humanized DR5 agonist monoclonal antibody, with gemcitabine proved to be more efficacious by providing a double hit to kill both CSCs and bulk tumor cells. The combination therapy produced remarkable reduction in pancreatic CSCs, tumor remissions, and significant improvements in time to tumor progression in a model that is considered more difficult to treat. These data provide the rationale to explore the DR5-directed therapies in combination with chemotherapy as a therapeutic option to improve the current standard of care for pancreatic cancer patients.
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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.