ArticleCancer research2020
HDAC6 Plays a Noncanonical Role in the Regulation of Antitumor Immune Responses, Dissemination, and Invasiveness of Breast Cancer.
Article in Cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 62 citations in OpenAlex.
- Macrophage-Centric Phenotypic Screening Identifies Tetrazolone-Based HDAC6 Inhibitors That Reprogram the Tumor Immune Microenvironment and Improve Immune Checkpoint Blockade.Journal of medicinal chemistry · 2026Article
- Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Design, Synthesis, and Biological Evaluation of Novel Triazine-Based Dual Histone Deacetylase/phosphatidylinositol 3-kinase Inhibitors for Breast Cancer Therapy.ChemMedChem · 2026Article
- Novel quinazoline-triazole-basedRSC advances · 2025Article
- HDAC6 and USP9X Control Glutamine Metabolism by Stabilizing GS to Promote Glioblastoma Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- HDAC6 facilitates LUAD progression by inducing EMT and enhancing macrophage polarization towards the M2 phenotype.NPJ precision oncology · 2025Article
- Histone acetylation modulators in breast cancer.Breast cancer research : BCR · 2025Review
- HDAC6 inhibition by ITF3756 modulates PD-L1 expression and monocyte phenotype: insights for a promising immune checkpoint blockade co-treatment therapy.Frontiers in immunology · 2025Article
- Pathogenic variants of TUBB8 cause oocyte spindle defects by disrupting with EB1/CAKP5 interactions and potential treatment targeting microtubule acetylation through HDAC6 inhibition.Clinical and translational medicine · 2025Article
- Advances of HDAC inhibitors in tumor therapy: potential applications through immune modulation.Frontiers in oncology · 2025Review
- The HDAC6 inhibitor AVS100 (SS208) induces a pro-inflammatory tumor microenvironment and potentiates immunotherapy.Science advances · 2024Article
- Phase separation of phospho-HDAC6 drives aberrant chromatin architecture in triple-negative breast cancer.Nature cancer · 2024Article
- Phase separation rewires chromatin in breast cancer.Nature cancer · 2024Article
- Cell therapy using ex vivo reprogrammed macrophages enhances antitumor immune responses in melanoma.Journal of experimental & clinical cancer research : CR · 2024Article
- HDAC6 Deletion Decreases Pristane-induced Inflammation.ImmunoHorizons · 2024Article
- Histone deacetylase 6 as a novel promising target to treat cardiovascular disease.Cancer innovation · 2024Review
- The Histone Deacetylase Family: Structural Features and Application of Combined Computational Methods.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Apigenin and its combination with Vorinostat induces apoptotic-mediated cell death in TNBC by modulating the epigenetic and apoptotic regulators and related miRNAs.Scientific reports · 2024Article
- Targeting HDAC6 improves anti-CD47 immunotherapy.Journal of experimental & clinical cancer research : CR · 2024Article
- A glimpse into novel acylations and their emerging role in regulating cancer metastasis.Cellular and molecular life sciences : CMLS · 2024Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Despite the outstanding clinical results of immune checkpoint blockade (ICB) in melanoma and other cancers, clinical trials in breast cancer have reported low responses to these therapies. Current efforts are now focused on improving the treatment efficacy of ICB in breast cancer using new combination designs such as molecularly targeted agents, including histone deacetylase inhibitors (HDACi). These epigenetic drugs have been widely described as potent cytotoxic agents for cancer cells. In this work, we report new noncanonical regulatory properties of ultra-selective HDAC6i over the expression and function of epithelial-mesenchymal transition pathways and the invasiveness potential of breast cancer. These unexplored roles position HDAC6i as attractive options to potentiate ongoing immunotherapeutic approaches. These new functional activities of HDAC6i involved regulation of the E-cadherin/STAT3 axis. Pretreatment of tumors with HDAC6i induced critical changes in the tumor microenvironment, resulting in improved effectiveness of ICB and preventing dissemination of cancer cells to secondary niches. Our results demonstrate for the first time that HDAC6i can both improve ICB antitumor immune responses and diminish the invasiveness of breast cancer with minimal cytotoxic effects, thus departing from the cytotoxicity-centric paradigm previously assigned to HDACi. SIGNIFICANCE: Ultraselective HDAC6 inhibitors can reduce tumor growth and invasiveness of breast cancer by noncanonical mechanisms unrelated to the previously cytotoxic properties attributed to HDAC inhibitors.
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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.