Istodax (romidepsin)

In this work, we discovered that the combination of class I histone deacetylase (HDAC) inhibitors, such as romidepsin, with a novel RNA helicase eIF4A inhibitor, des-methyl pateamine A (DMPatA), induces robust and persistent hyperacetylation, significantly exceeding the levels and duration observed with HDAC inhibitor monotherapy...The combination does not appear to induce known resistance mechanisms such as drug efflux; elevated MYC expression, rather than inducing resistance, sensitizes PDAC cells to treatment. These studies support translation of this synergistic combination to the clinic.

P2, N=47, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Jul 2026 --> Oct 2025 | Trial primary completion date: Jul 2026 --> Oct 2025

Based on the mechanism of PFKL facilitates the efficacy of romidepsin, we developed a therapeutic peptide, PFKL-552-572-R8, which significantly enhances the antitumor effect of romidepsin both in vitro and in vivo. Our findings reveal that spatiotemporal regulation confers a moonlight function to PFKL as an endogenous HDAC inhibitor to maintain the stability of epigenetic modifications and highlight PFKL as a promising therapeutic target for enhancing the clinical utility of HDACi in solid tumors.

P1/2, N=51, Active, not recruiting, Priyanka Sharma | Trial completion date: Jul 2025 --> Jul 2026 | Trial primary completion date: Dec 2024 --> Jul 2026

P1/2, N=75, Completed, GWT-TUD GmbH | Active, not recruiting --> Completed

Notably, treatment with low-dose romidepsin, an FDA-approved inhibitor targeting HDAC1, a core component of the NuRD complex, effectively restored NK and T cell-mediated killing in cancer cells with high ZNF296 expression. Collectively, these findings establish ZNF296 as a key regulator of immune evasion, driving resistance to both NK and T cell-mediated antitumor immunity, and highlight its potential as a therapeutic target to overcome immune resistance in epithelial cancers.

We report a case of a 66-year-old female with a history of stage IIB folliculotrophic mycosis fungoides with large cell transformation, currently being treated with romidepsin and gemcitabine, transferred to our institution due to worsening cutaneous involvement. Diagnosis is based on the presence of vesiculobullous lesions among typical lesions of mycosis fungoides, histopathologic features consistent with mycosis fungoides, and negative evaluation for other causes of vesiculobullous lesions such as infection and autoimmune blistering diseases. Recognition is important as mycosis fungoides bullosa carries poor prognosis, with 50% of reported patients expiring within 1 year of bullae appearance.

P1, N=23, Completed, Ohio State University Comprehensive Cancer Center | Active, not recruiting --> Completed | Trial completion date: Sep 2025 --> Jun 2025

Collectively, our studies established a previously unrecognized GATA2/GATA3-FOXA1-HER3 axis as a key regulatory network in BLBC progression. We provide strong experimental data supporting that the two HDACi, Romidepsin and Panobinostat may be repurposed as effective therapeutic agents for BLBC.

Our findings put forward the intricate crosstalk between epigenetics, metabolism, and immune response in cancer. The broad action of romidepsin on distinct cellular functions highlights its therapeutic potential for HCC treatment.

We reveal that the inhibition of HDAC1/HDAC2 with the clinically advanced HDACi romidepsin, the experimental HDACi entinostat and MERCK60, and genetic depletion of HDAC1/HDAC2 induce apoptosis and long-term growth arrest of primary and permanent MPN cells in vitro and in vivo. Moreover, HDAC1 is an adverse prognostic factor in patients with acute myeloid leukemia (n = 150, p = 0.02), being a possible complication of MPNs. These insights reveal a previously unappreciated link between HDAC1/HDAC2 as key molecular targets, the still undefined regulation of cytoplasmic-to-nuclear signaling by HDACs, and how HDACi kill JAK2V617F-positive cells from MPN patients and mice with JAK2V617F in vitro and in vivo.

Although there are many highly selective and potent HDAC inhibitors (such as romidepsin and belinostat), few HAT inhibitors are undergoing clinical trials. Studies have shown that CBP is highly expressed and activated in a variety of different tumors; therefore, its inhibitors have attracted increasing research attention. In this review, we discuss the importance of the structure of CBP in the development of potential inhibitors to provide a reference for the development of new selective CBP inhibitors.