ArticleCancer research2013
Hypomethylating therapy in an aggressive stroma-rich model of pancreatic carcinoma.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- Differentiation therapy and the mechanisms that terminate cancer cell proliferation without harming normal cells.Cell death & disease · 2018Pooled it
- Phase 2 study of azacitidine plus pembrolizumab as second-line treatment in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma.The oncologist · 2026Trial
- An open-label, single-arm, phase I/II study of lower-dose decitabine based therapy in patients with advanced hepatocellular carcinoma.Oncotarget · 2015Trial
- Epigenetic modulation to overcome immune suppression in pancreatic cancer.Clinical epigenetics · 2026Review
- The role of epigenetic modifications in cancer-associated fibroblasts.Frontiers in medicine · 2026Review
- The Spatiotemporal Heterogeneity of Tumor-Associated Stromal Cells: Reprogramming Plasticity to Unlock Precision Cancer Immunotherapy.Cancer communications (London, England) · 2026Review
- Article
- Optimization of a mouse model of pancreatic cancer to simulate the human phenotypes of metastasis and cachexia.BMC cancer · 2024Article
- Natural killer cells for pancreatic cancer immunotherapy: Role of nanoparticles.Cancer letters · 2023Article
- Deoxyribonucleic acid methylation driven aberrations in pancreatic cancer-related pathways.World journal of gastrointestinal oncology · 2023Review
- Methylation across the central dogma in health and diseases: new therapeutic strategies.Signal transduction and targeted therapy · 2023Review
- Epigenetic regulation of cancer-associated fibroblast heterogeneity.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Epigenetics in Pancreatic Ductal Adenocarcinoma: Impact on Biology and Utilization in Diagnostics and Treatment.Cancers · 2022Review
- Targeting myeloid suppressive cells revives cytotoxic anti-tumor responses in pancreatic cancer.iScience · 2022Article
- Epigenetic regulation of pancreatic adenocarcinoma in the era of cancer immunotherapy.Journal of gastroenterology · 2022Review
- EMT alterations in the solute carrier landscape uncover SLC22A10/A15 imposed vulnerabilities in pancreatic cancer.iScience · 2022Article
- Epigenetic Therapeutic Strategies to Target Molecular and Cellular Heterogeneity in Pancreatic Cancer.Visceral medicine · 2022Review
- Emerging Role of Epigenetic Alterations as Biomarkers and Novel Targets for Treatments in Pancreatic Ductal Adenocarcinoma.Cancers · 2022Review
- Pancreatic cancer cells render tumor-associated macrophages metabolically reprogrammed by a GARP and DNA methylation-mediated mechanism.Signal transduction and targeted therapy · 2021Article
- Epigenetic Reprogramming of Tumor-Associated Fibroblasts in Lung Cancer: Therapeutic Opportunities.Cancers · 2021Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that resists current treatments. To test epigenetic therapy against this cancer, we used the DNA demethylating drug 5-aza-2'-deoxycytidine (DAC) in an aggressive mouse model of stromal rich PDAC (KPC-Brca1 mice). In untreated tumors, we found globally decreased 5-methyl-cytosine (5-mC) in malignant epithelial cells and in cancer-associated myofibroblasts (CAF), along with increased amounts of 5-hydroxymethyl-cytosine (5-HmC) in CAFs, in progression from pancreatic intraepithelial neoplasia to PDAC. DAC further reduced DNA methylation and slowed PDAC progression, markedly extending survival in an early-treatment protocol and significantly though transiently inhibiting tumor growth when initiated later, without adverse side effects. Escaping tumors contained areas of sarcomatoid transformation with disappearance of CAFs. Mixing-allografting experiments and proliferation indices showed that DAC efficacy was due to inhibition of both the malignant epithelial cells and the CAFs. Expression profiling and immunohistochemistry highlighted DAC induction of STAT1 in the tumors, and DAC plus IFN-γ produced an additive antiproliferative effect on PDAC cells. DAC induced strong expression of the testis antigen deleted in azoospermia-like (DAZL) in CAFs. These data show that DAC is effective against PDAC in vivo and provide a rationale for future studies combining hypomethylating agents with cytokines and immunotherapy.
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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.