ArticleCancers2019
Selective Inhibition of Histone Deacetylases 1/2/6 in Combination with Gemcitabine: A Promising Combination for Pancreatic Cancer Therapy.
Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- A phase I/II study of ivaltinostat combined with gemcitabine and erlotinib in patients with untreated locally advanced or metastatic pancreatic adenocarcinoma.International journal of cancer · 2022Trial
- ER-phagy mediates the anti-tumoral synergism between HDAC inhibition and chemotherapy.Cell communication and signaling : CCS · 2025Article
- Selective HDAC6 Inhibition Has the Potential for Anti-Cancer Effect in Renal Cell Carcinoma.Journal of personalized medicine · 2024Article
- Novel Histone Deacetylase (HDAC) Inhibitor Induces Apoptosis and Suppresses Invasion via E-Cadherin Upregulation in Pancreatic Ductal Adenocarcinoma (PDAC).Pharmaceuticals (Basel, Switzerland) · 2024Article
- Genomic analysis reveals HDAC1 regulates clinically relevant transcriptional programs in Pancreatic cancer.BMC cancer · 2023Article
- Mocetinostat activates Krüppel-like factor 4 and protects against tissue destruction and inflammation in osteoarthritis.JCI insight · 2023Article
- Correlating Basal Gene Expression across Chemical Sensitivity Data to Screen for Novel Synergistic Interactors of HDAC Inhibitors in Pancreatic Carcinoma.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Targeting HDAC6 to Overcome Autophagy-Promoted Anti-Cancer Drug Resistance.International journal of molecular sciences · 2022Review
- Histone modifiers at the crossroads of oncolytic and oncogenic viruses.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Targeting pancreatic cancer immune evasion by inhibiting histone deacetylases.World journal of gastroenterology · 2022Review
- The histone deacetylase inhibitor M344 as a multifaceted therapy for pancreatic cancer.PloS one · 2022Article
- Clinical Utility of Epigenetic Changes in Pancreatic Adenocarcinoma.Epigenomes · 2021Review
- Article
- Improved HDAC Inhibition, Stronger Cytotoxic Effect and Higher Selectivity against Leukemias and Lymphomas of Novel, Tricyclic Vorinostat Analogues.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Article
- A G-Quadruplex-Binding Small Molecule and the HDAC Inhibitor SAHA (Vorinostat) Act Synergistically in Gemcitabine-Sensitive and Resistant Pancreatic Cancer Cells.Molecules (Basel, Switzerland) · 2020Article
- PAICS contributes to gastric carcinogenesis and participates in DNA damage response by interacting with histone deacetylase 1/2.Cell death & disease · 2020Article
- Expression of HDAC1 and RBBP4 correlate with clinicopathologic characteristics and prognosis in breast cancer.International journal of clinical and experimental pathology · 2020Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) has a five-year survival rate of <10% due in part to a lack of effective therapies. Pan-histone deacetylase (HDAC) inhibitors have shown preclinical efficacy against PDAC but have failed in the clinic due to toxicity. Selective HDAC inhibitors may reduce toxicity while retaining therapeutic efficacy. However, their use requires identification of the specific HDACs that mediate the therapeutic effects of HDAC inhibitors in PDAC. We determined that the HDAC1/2/3 inhibitor Mocetinostat synergizes with the HDAC4/5/6 inhibitor LMK-235 in a panel of PDAC cell lines. Furthermore, while neither drug alone synergizes with gemcitabine, the combination of Mocetinostat, LMK-235, and gemcitabine showed strong synergy. Using small interfering (si)RNA-mediated knockdown, this synergy was attributed to inhibition of HDACs 1, 2, and 6. Pharmacological inhibition of HDACs 1 and 2 with Romidepsin and HDAC6 with ACY-1215 also potently synergized with gemcitabine in a panel of PDAC cell lines, and this drug combination potentiated the antitumor effects of gemcitabine against PDAC xenografts in vivo. Collectively, our data show that inhibition of multiple HDACs is required for therapeutic effects of HDAC inhibitors and support the development of novel strategies to inhibit HDACs 1, 2, and 6 for PDAC therapy.
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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.