ArticleScience advances2024
The HDAC6 inhibitor AVS100 (SS208) induces a pro-inflammatory tumor microenvironment and potentiates immunotherapy.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Aging reprograms the functional, epigenetic, and metabolic landscape of macrophages.Research square · 2026Article
- 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
- The impactful role of the HDACs in the regulation of gene expression and as targets for disease therapy.Science advances · 2026Review
- Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Epigenetic remodeling via HDAC6 inhibition amplifies anti-tumoral immune responses in myeloid leukemia cells.Cell death & disease · 2026Article
- HDAC6 orchestrates metastatic and immunosuppressive programs in small cell lung cancer through S100A2-TGF-β/SMAD and CSF1R signaling.Molecular cancer · 2026Article
- Role of HDAC6 in carcinomas.Discover oncology · 2026Review
- Epigenetic modifiers to enhance the efficacy of immune checkpoint inhibitors for the treatment of melanoma.Translational oncology · 2025Review
- HDAC6 facilitates LUAD progression by inducing EMT and enhancing macrophage polarization towards the M2 phenotype.NPJ precision oncology · 2025Article
- The epigenetic hallmarks of immune cells in cancer.Molecular cancer · 2025Review
- The regulatory mechanisms and treatment of HDAC6 in immune dysregulation diseases.Frontiers in immunology · 2025Review
- Targeting tumor-associated macrophages in colon cancer: mechanisms and therapeutic strategies.Frontiers in immunology · 2025Review
- Histone deacetylases in the regulation of cell death and survival mechanisms in resistant BRAF-mutant cancers.Cancer drug resistance (Alhambra, Calif.) · 2025Review
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Authors and funding
12 authors.
Funding
Abstract
Histone deacetylase 6 (HDAC6) inhibition is associated with an increased pro-inflammatory tumor microenvironment and antitumoral immune responses. Here, we show that the HDAC6 inhibitor AVS100 (SS208) had an antitumoral effect in SM1 melanoma and CT26 colon cancer models and increased the efficacy of anti-programmed cell death protein 1 treatment, leading to complete remission in melanoma and increased response in colon cancer. AVS100 treatment increased pro-inflammatory tumor-infiltrating macrophages and CD8 effector T cells with an inflammatory and T cell effector gene signature. Acquired T cell immunity and long-term protection were evidenced as increased immunodominant T cell clones after AVS100 treatment. Last, AVS100 showed no mutagenicity, toxicity, or adverse effects in preclinical good laboratory practice studies, part of the package that has led to US Food and Drug Administration clearance of an investigational new drug application for initiating clinical trials. This would be a first-in-human combination therapy of pembrolizumab with HDAC6 inhibition for locally advanced or metastatic solid tumors.
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