ArticleCancer biology & therapy2015
Synergistic anti-leukemic interactions between panobinostat and MK-1775 in acute myeloid leukemia ex vivo.
Article in Cancer biology & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- An update of predictive biomarkers related to WEE1 inhibition in cancer therapy.Journal of cancer research and clinical oncology · 2024Pooled it
- The Functional Transcriptomic Landscape Informs Therapeutic Strategies in Multiple Myeloma.Cancer research · 2025Article
- Synergistic effect of adavosertib and fimepinostat on acute myeloid leukemia cells by enhancing the induction of DNA damage.Investigational new drugs · 2024Article
- Targeting the DNA damage response in hematological malignancies.Frontiers in oncology · 2024Review
- Phase 1 study of belinostat and adavosertib in patients with relapsed or refractory myeloid malignancies.Cancer chemotherapy and pharmacology · 2023Article
- Ricolinostat enhances adavosertib‑induced mitotic catastrophe in TP53‑mutated head and neck squamous cell carcinoma cells.International journal of oncology · 2022Article
- The paradigm of drug resistance in cancer: an epigenetic perspective.Bioscience reports · 2022Review
- Inhibitors of class I HDACs and of FLT3 combine synergistically against leukemia cells with mutant FLT3.Archives of toxicology · 2022Article
- The HDAC and PI3K dual inhibitor CUDC-907 synergistically enhances the antileukemic activity of venetoclax in preclinical models of acute myeloid leukemia.Haematologica · 2021Article
- Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy.Signal transduction and targeted therapy · 2020Review
- A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target.Journal of hematology & oncology · 2020Review
- 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
- Preclinical evaluation of the combination of AZD1775 and irinotecan against selected pediatric solid tumors: A Pediatric Preclinical Testing Consortium report.Pediatric blood & cancer · 2020Article
- Understanding the Mechanisms by Which Epigenetic Modifiers Avert Therapy Resistance in Cancer.Frontiers in oncology · 2020Review
- HDAC Inhibitors in Acute Myeloid Leukemia.Cancers · 2019Review
- Antileukemic activity and mechanism of action of the novel PI3K and histone deacetylase dual inhibitor CUDC-907 in acute myeloid leukemia.Haematologica · 2019Article
- Challenges and Opportunities for Childhood Cancer Drug Development.Pharmacological reviews · 2019Review
- Targeting WEE1 to enhance conventional therapies for acute lymphoblastic leukemia.Journal of hematology & oncology · 2018Article
- Recent Advances of Cell-Cycle Inhibitor Therapies for Pediatric Cancer.Cancer research · 2017Review
- The cell cycle checkpoint inhibitors in the treatment of leukemias.Journal of hematology & oncology · 2017Review
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MK-1775 is the first-in-class selective Wee1 inhibitor which has been demonstrated to synergize with CHK1 inhibitors in various malignancies. In this study, we report that the pan-histone deacetylase inhibitor (HDACI) panobinostat synergizes with MK-1775 in acute myeloid leukemia (AML), a malignancy which remains a clinical challenge and requires more effective therapies. Using both AML cell line models and primary patient samples, we demonstrated that panobinostat and MK-1775 synergistically induced proliferation arrest and cell death. We also demonstrated that panobinostat had equal anti-leukemic activities against primary AML blasts derived from patients either at initial diagnosis or at relapse. Interestingly, treatment with panobinostat alone or in combination with MK-1775 resulted in decreased Wee1 protein levels as well as downregulation of the CHK1 pathway. shRNA knockdown of CHK1 significantly sensitized AML cells to MK-1775 treatment, while knockdown of Wee1 significantly enhanced both MK-1775- and panobinostat-induced cell death. Our results demonstrate that panobinostat synergizes with MK-1775 in AML cells, at least in part through downregulation of CHK1 and/or Wee1, providing compelling evidence for the clinical development of the combination treatment in AML.
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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.