ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Entinostat Enhances the Efficacy of Chemotherapy in Small Cell Lung Cancer Through S-phase Arrest and Decreased Base Excision Repair.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- A Multi-Omics Framework Reveals Tumor Heterogeneity and Predicts Therapeutic Targets in Renal Cell Carcinoma.International journal of molecular sciences · 2026Article
- Methodological Landscape of DNA Damage Response Detection: From Conventional Assays to Future Innovations.Current issues in molecular biology · 2026Review
- Exploring the Impact of Nanotherapeutics on Histone H3 and H4 Acetylation Enrichment in Cancer Epigenome: A Systematic Scoping Synthesis.Epigenomes · 2025Review
- Inhibition of YB-1 phosphorylation enhances cisplatin activity and disrupts cell division in pleural mesothelioma.British journal of cancer · 2025Article
- Assessing the selective impact of histone modifying drugs on adenoid cystic carcinoma cells and their stem cell counterparts.BMC cancer · 2025Article
- Irinotecan alleviates chemoresistance to anthracyclines through the inhibition of AARS1-mediated BLM lactylation and homologous recombination repair.Signal transduction and targeted therapy · 2025Article
- Dual Targeting EZH2 and Histone Deacetylases in Human Uterine Sarcoma Cells Under Both 2D and 3D Culture Conditions.Journal of cellular and molecular medicine · 2025Article
- Comparative Analysis of Transcriptomic and Proteomic Expression between Two Non-Small Cell Lung Cancer Subtypes.Journal of proteome research · 2025Article
- Acquired vulnerability against EGF receptor inhibition in gastric cancer promoted by class I histone deacetylase inhibitor entinostat.Neoplasia (New York, N.Y.) · 2025Article
- Advancing Epigenetic Combination Therapy in Oncology: Multifunctional Nano-Drug Delivery Systems for Synergistic Efficacy and Precision Modulation.International journal of nanomedicine · 2025Review
- Niche-specific epigenetic interventions in the spatially heterogeneous glioblastoma microenvironmental landscape: strategies for radiotherapy enhancement.Frontiers in molecular biosciences · 2025Review
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Review
- Small cell lung cancer: emerging subtypes, signaling pathways, and therapeutic vulnerabilities.Experimental hematology & oncology · 2024Review
- Nanocarrier mediated entinostat and oxaliplatin combination therapy displayed enhanced efficacy against pancreatic cancer.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- NUSAP1 is Upregulated by Estrogen to Promote Lung Adenocarcinoma Growth and Serves as a Therapeutic Target.International journal of biological sciences · 2024Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
purposeAcquired chemoresistance is a frequent event in small cell lung cancer (SCLC), one of the deadliest human malignancies. Histone deacetylase inhibitors (HDACi) have been shown to synergize with different chemotherapeutic agents including cisplatin. Accordingly, we aimed to investigate the dual targeting of HDAC inhibition and chemotherapy in SCLC. EXPERIMENTAL
designThe efficacy of HDACi and chemotherapy in SCLC was investigated both in vitro and in vivo. Synergistic drug interactions were calculated based on the HSA model (Combenefit software). Results from the proteomic analysis were confirmed via ICP-MS, cell-cycle analysis, and comet assays.
resultsSingle entinostat- or chemotherapy significantly reduced cell viability in human neuroendocrine SCLC cells. The combination of entinostat with either cisplatin, carboplatin, irinotecan, epirubicin, or etoposide led to strong synergy in a subset of resistant SCLC cells. Combination treatment with entinostat and cisplatin significantly decreased tumor growth in vivo. Proteomic analysis comparing the groups of SCLC cell lines with synergistic and additive response patterns indicated alterations in cell-cycle regulation and DNA damage repair. Cell-cycle analysis revealed that cells exhibiting synergistic drug responses displayed a shift from G1 to S-phase compared with cells showing additive features upon dual treatment. Comet assays demonstrated more DNA damage and decreased base excision repair in SCLC cells more responsive to combination therapy.
conclusionsIn this study, we decipher the molecular processes behind synergistic interactions between chemotherapy and HDAC inhibition. Moreover, we report novel mechanisms to overcome drug resistance in SCLC, which may be relevant to increasing therapeutic success.
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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.