ArticleJournal of cellular and molecular medicine2019
CUDC-907 blocks multiple pro-survival signals and abrogates microenvironment protection in CLL.
Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The trial behind it
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- The tumor microenvironment in leukemia: molecular pathways of immune evasion.Frontiers in immunology · 2026Review
- S-adenosylmethionine addiction confers sensitivity to methionine restriction inHaematologica · 2025Article
- Targeted Degradation of Class 1 HDACs With PROTACs is Highly Effective at Inducing DLBCL Cell Death.EJHaem · 2025Article
- Molecular mechanisms of unique therapeutic potential of CUDC-907 for MEF2D fusion-driven BCP-ALL.Signal transduction and targeted therapy · 2025Article
- HGF/c-MET axis contributes to CLL cell survival by regulating multiple mechanisms making it a potential therapeutic target for CLL treatment.Frontiers in pharmacology · 2025Article
- MYC Oncogene: A Druggable Target for Treating Cancers with Natural Products.Aging and disease · 2024Review
- The dual HDAC and PI3K inhibitor, CUDC‑907, inhibits tumor growth and stem‑like properties by suppressing PTX3 in neuroblastoma.International journal of oncology · 2024Article
- Article
- NF-kB and the CLL microenvironment.Frontiers in oncology · 2023Review
- MYC: a multipurpose oncogene with prognostic and therapeutic implications in blood malignancies.Journal of hematology & oncology · 2021Review
- Antitumor activity and mechanism of resistance of the novel HDAC and PI3K dual inhibitor CUDC-907 in pancreatic cancer.Cancer chemotherapy and pharmacology · 2021Article
- Pluripotent stem cell-based screening identifies CUDC-907 as an effective compound for restoring the in vitro phenotype of Nakajo-Nishimura syndrome.Stem cells translational medicine · 2021Article
- Combating TKI resistance in CML by inhibiting the PI3K/Akt/mTOR pathway in combination with TKIs: a review.Medical oncology (Northwood, London, England) · 2021Review
- Therapeutic Potential of CUDC-907 (Fimepinostat) for Hepatocarcinoma Treatment Revealed by Tumor Spheroids-Based Drug Screening.Frontiers in pharmacology · 2021Article
- Dual Kinase Targeting in Leukemia.Cancers · 2021Review
- CUDC-907 enhances TRAIL-induced apoptosis through upregulation of DR5 in breast cancer cells.Journal of cell communication and signaling · 2020Article
- Histone Deacetylase Inhibitors as Multitarget-Directed Epi-Drugs in Blocking PI3K Oncogenic Signaling: A Polypharmacology Approach.International journal of molecular sciences · 2020Review
- Effect of dual inhibition of histone deacetylase and phosphatidylinositol-3 kinase in Philadelphia chromosome-positive leukemia cells.Cancer chemotherapy and pharmacology · 2020Article
- Epigenetic polypharmacology: A new frontier for epi-drug discovery.Medicinal research reviews · 2020Review
- Regulation of Chemokines and Cytokines by Histone Deacetylases and an Update on Histone Decetylase Inhibitors in Human Diseases.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
CUDC-907, a dual PI3K/HDAC inhibitor, has been proposed to have therapeutic potential in hematopoietic malignancies. However, the molecular mechanisms of its effects in chronic lymphocytic leukaemia (CLL) remain elusive. We show that CLL cells are sensitive to CUDC-907, even under conditions similar to the protective microenvironment of proliferation centres. CUDC-907 inhibited PI3K/AKT and HDAC activity, as expected, but also suppressed RAF/MEK/ERK and STAT3 signalling and reduced the expression of anti-apoptotic BCL-2 family proteins BCL-2, BCL-xL, and MCL-1. Moreover, CUDC-907 downregulated cytokines BAFF and APRIL and their receptors BAFFR, TACI, and BCMA, thus blocking BAFF-induced NF-κB signalling. T cell chemokines CCL3/4/17/22 and phosphorylation of CXCR4 were also reduced by CUDC-907. These data indicated that CUDC-907 abrogates different protective signals and suggested that it might sensitize CLL cells to other drugs. Indeed, combinations of low concentrations of CUDC-907 with inhibitors of BCL2, BTK, or the NF-κB pathway showed a potent synergistic effect. Our data indicate that, apart from its known functions, CUDC-907 blocks multiple pro-survival pathways to overcome microenvironment protection in CLL cells. This provides a rationale to evaluate the clinical relevance of CUDC-907 in combination therapies with other targeted inhibitors.
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Registered trials
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