ArticleCancer letters2015
Synergistic antitumor interactions between MK-1775 and panobinostat in preclinical models of pancreatic cancer.
Article in Cancer letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- LBH589 reduces oxidized mitochondrial DNA and suppresses NLRP3 inflammasome activation to relieve pulmonary inflammation.PloS one · 2025Article
- Synergistic Efficacy of CDK4/6 Inhibitor Abemaciclib and HDAC Inhibitor Panobinostat in Pancreatic Cancer Cells.Cancers · 2024Article
- Combination of PARP and WEE1 inhibitorsOncology reports · 2023Article
- Targeting replication stress in cancer therapy.Nature reviews. Drug discovery · 2023Review
- Article
- Antitumor activity and mechanism of resistance of the novel HDAC and PI3K dual inhibitor CUDC-907 in pancreatic cancer.Cancer chemotherapy and pharmacology · 2021Article
- Pharmacological Inhibition of WEE1 Potentiates the Antitumoral Effect of theInternational journal of molecular sciences · 2020Article
- CUDC-907, a novel dual PI3K and HDAC inhibitor, in prostate cancer: Antitumour activity and molecular mechanism of action.Journal of cellular and molecular medicine · 2020Article
- Wee1 Inhibitor AZD1775 Effectively Inhibits the Malignant Phenotypes of Esophageal Squamous Cell CarcinomaFrontiers in pharmacology · 2019Article
- Wee1 kinase inhibitor MK-1775 induces apoptosis of acute lymphoblastic leukemia cells and enhances the efficacy of doxorubicin involving downregulation of Notch pathway.Oncology letters · 2018Article
- Augmented antitumor activity by olaparib plus AZD1775 in gastric cancer through disrupting DNA damage repair pathways and DNA damage checkpoint.Journal of experimental & clinical cancer research : CR · 2018Article
- Wee1 Inhibitor AZD1775 Combined with Cisplatin Potentiates Anticancer Activity against Gastric Cancer by Increasing DNA Damage and Cell Apoptosis.BioMed research international · 2018Article
- Suppression of Sirt1 sensitizes lung cancer cells to WEE1 inhibitor MK-1775-induced DNA damage and apoptosis.Oncogene · 2017Article
- Directing the use of DDR kinase inhibitors in cancer treatment.Expert opinion on investigational drugs · 2017Review
- Targeting ERK enhances the cytotoxic effect of the novel PI3K and mTOR dual inhibitor VS-5584 in preclinical models of pancreatic cancer.Oncotarget · 2017Article
- Inhibition of ATR potentiates the cytotoxic effect of gemcitabine on pancreatic cancer cells through enhancement of DNA damage and abrogation of ribonucleotide reductase induction by gemcitabine.Oncology reports · 2017Article
- Cell cycle proteins as promising targets in cancer therapy.Nature reviews. Cancer · 2017Review
- ROS attenuates the antitumor effect of Raddeanin on ovarian cancer cells Skov3.International journal of clinical and experimental pathology · 2017Article
- WEE1 inhibition in pancreatic cancer cells is dependent on DNA repair status in a context dependent manner.Scientific reports · 2016Article
- Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Pancreatic cancer remains a clinical challenge, thus new therapies are urgently needed. The selective Wee1 inhibitor MK-1775 has demonstrated promising results when combined with DNA damaging agents, and more recently with CHK1 inhibitors in various malignancies. We have previously demonstrated that treatment with the pan-histone deacetylase inhibitor panobinostat (LBH589) can cause down-regulation of CHK1. Accordingly, we investigated using panobinostat to down-regulate CHK1 in combination with MK-1775 to enhance cell death in preclinical pancreatic cancer models. We demonstrate that MK-1775 treatment results in increased H2AX phosphorylation, indicating increased DNA double-strand breaks, and activation of CHK1, which are both dependent on CDK activity. Combination of MK-1775 and panobinostat resulted in synergistic antitumor activity in six pancreatic cancer cell lines. Finally, our in vivo study using a pancreatic xenograft model reveals promising cooperative antitumor activity between MK-1775 and panobinostat. Our study provides compelling evidence that the combination of MK-1775 and panobinostat has antitumor activity in preclinical models of pancreatic cancer and supports the clinical development of panobinostat in combination with MK-1775 for the treatment of this deadly disease.
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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.