ArticleClinical epigenetics2019
Combination treatment strategy for pancreatic cancer involving the novel HDAC inhibitor MPT0E028 with a MEK inhibitor beyond K-Ras status.
Article in Clinical epigenetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 48 citations in OpenAlex.
- Pancreatic ductal adenocarcinoma: integrating molecular insights for targeted interventions.Signal transduction and targeted therapy · 2026Review
- Clinical progress and functional modalities of HDAC inhibitor-based combination therapies in cancer treatment.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- Review
- A Histone Methylation-MAPK Signaling Axis Drives Durable Epithelial-Mesenchymal Transition in Hypoxic Pancreatic Cancer.Cancer research · 2024Article
- Nanocarrier mediated entinostat and oxaliplatin combination therapy displayed enhanced efficacy against pancreatic cancer.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Role of a novel circRNA-CGNL1 in regulating pancreatic cancer progression via NUDT4-HDAC4-RUNX2-GAMT-mediated apoptosis.Molecular cancer · 2024Article
- Article
- Targeting KRAS for the potential treatment of pancreatic ductal adenocarcinoma: Recent advancements provide hope (Review).Oncology reports · 2023Review
- Targeting histone deacetylases for cancer therapy: Trends and challenges.Acta pharmaceutica Sinica. B · 2023Review
- Histone Modifications Represent a Key Epigenetic Feature of Epithelial-to-Mesenchyme Transition in Pancreatic Cancer.International journal of molecular sciences · 2023Review
- Establishment and validation of a ubiquitination-related gene signature associated with prognosis in pancreatic duct adenocarcinoma.Frontiers in immunology · 2023Article
- Pyroptosis-related genes regulate proliferation and invasion of pancreatic cancer and serve as the prognostic signature for modeling patient survival.Discover oncology · 2022Article
- Article
- Conquering oncogenic KRAS and its bypass mechanisms.Theranostics · 2022Review
- An overview of genetic mutations and epigenetic signatures in the course of pancreatic cancer progression.Cancer metastasis reviews · 2021Review
- Bioinformatics Data Mining Repurposes the JAK2 (Janus Kinase 2) Inhibitor Fedratinib for Treating Pancreatic Ductal Adenocarcinoma by Reversing theJournal of personalized medicine · 2020Article
- Review
- Targeting MAPK Signaling in Cancer: Mechanisms of Drug Resistance and Sensitivity.International journal of molecular sciences · 2020Review
- Synergistic lethal mutagenesis of hepatitis C virus.Antimicrobial agents and chemotherapy · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOncogenic K-Ras signaling highly relies on the canonical Ras/MEK/ERK pathway to contribute to pancreatic cancer progression. However, numerous efforts of MEK inhibitors have failed to provide an optimal antitumor effect for pancreatic cancer in practice. The aim of the present work was to develop a more efficacious therapeutic intervention for MEK inhibitors through combination with histone deacetylase (HDAC) inhibitor MPT0E028.
methodsThe effects of combined therapy on cell viability, apoptosis, protein, and RNA expressions were determined by MTT assay, flow cytometry, western blotting, and quantitative PCR analysis. The AsPC-1 xenograft was used to assess antitumor effects in vivo.
resultsThe co-administration of MPT0E028 and MEK inhibitor yielded synergistic effects on cell viability suppression both in K-Ras mutated and wild-type pancreatic cancer cells and also markedly triggered cell apoptosis. Surprisingly, ERK and epidermal growth factor receptor (EGFR) were activated by the long-term and low-concentration treatment of MPT0E028 or another HDAC inhibitor alone. Whereas, the pharmacological attenuation of ERK signaling dramatically abolished the MPTE028-induced p-ERK and EGFR expression. Overexpression of HDAC4, HDAC6, and MEK, respectively, reversed the cell death induced by the combined treatment. Finally, the combined treatment decreased the tumor volume in an AsPC-1 xenograft model compared to each individual treatment alone.
conclusionsThe synergistic anti-survival effect of the combination was suggested to occur via compensation of the MEK inhibitor for activated ERK. Our results indicate that this combination strategy could benefit patients with pancreatic cancer beyond K-Ras status.
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