Istodax (romidepsin)

High-throughput drug screening identifies FK228 and thioguanine as promising therapeutic candidates, both of which show in vivo efficacy and are validated in PTEN-deleted organoids. Together, these results establish MEPP as a platform for studying PTEN-deleted ovarian cancer and provide a strategy for generating clinically relevant tumor models through targeted gene editing.

In vitro we identified that romidepsin synergizes with doxorubicin and etoposide and that it increases the efficacy of the standard of care combinations VDC/IE. In vivo, the combination of romidepsin and ifosfamide/etoposide (IE) leads to a significant decrease in tumor volume compared to that of IE alone. Our data indicates that romidepsin improves efficacy of chemotherapeutic agents in vitro and leads to a decreased tumor volume in vivo, suggesting that the addition of romidepsin may improve upfront treatment in ES patients.

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.