guadecitabine (SGI-110)

P1, N=60, Active, not recruiting, Royal Marsden NHS Foundation Trust | Recruiting --> Active, not recruiting | N=34 --> 60

Pt resistance in HGSC is associated with epigenetic modifications and hypomethylating agents (HMAs) have been studied as carboplatin resensitizing agents...The Pt-resistant patients were enrolled in NCT02901899 clinical trial testing guadecitabine and the PD-1 inhibitor pembrolizumab...We propose new DMLs associated with Pt-naive versus Pt-resistant HGSC. These findings can lead to new biomarkers for HGSC.

P2, N=19, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Jan 2027

Guadecitabine, a hypomethylating agent (HMA), has shown promising clinical activity when combined with carboplatin in preclinical models. Methylome changes in peripheral blood mononuclear cell (PBMCs) from small cell lung cancer (SCLC) patients treated with an epigenetic therapy revealed global hypomethylation and altered cancer signaling processes associated with tumor progression, immune response, therapy resistance and significant change in the proportion of immune cells. Integrating blood-based methylation biomarkers into clinical trials of epigenetic therapy and methylomic analysis of PBMCs provides direct monitoring of treatment effects in cancer patients, which may improve patient selection and enable real-time response assessment in patients receiving hypomethylating agents.

P1/2, N=33, Active, not recruiting, University of Southern California | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

P1, N=55, Active, not recruiting, University of Southern California | Trial completion date: Dec 2025 --> Jul 2026

DNA methyltransferase inhibitors (e.g., decitabine, guadecitabine) have shown promise in attenuating osteoclast differentiation, while histone deacetylase inhibitors display context-dependent effects on tumor progression and bone remodeling...Together, these advances position epigenetic modulation as a promising axis in precision oncology aimed at interrupting the pathological crosstalk between tumor cells and the bone microenvironment. This review synthesizes current mechanistic understanding, evaluates the therapeutic landscape, and outlines the translational challenges ahead in leveraging epigenetic science to prevent and treat bone metastases.

P1, N=28, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jul 2025 --> Jul 2026 | Trial primary completion date: Jul 2025 --> Jul 2026

P1/2, N=33, Active, not recruiting, University of Southern California | Trial completion date: Nov 2025 --> Dec 2026 | Trial primary completion date: Nov 2024 --> Dec 2025

P1/2, N=12, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | N=75 --> 12

P1, N=55, Active, not recruiting, University of Southern California | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Mar 2021 --> Apr 2024

Improving the treatment schedules, increasing isoform specificity, reducing toxicity, and utilizing genome-wide analyses of CRISPR-based editing to create personalized epigenetic therapies tailored to individual patient needs are promising strategies for enhancing therapeutic outcomes. This review discusses the interaction between DNMT regulators and DNMT1, its binding partners, the connection between DNA methylation and tumors, how these processes contribute to tumor development, and DNMT inhibitors' advancements and pharmacological properties.