Furthermore, our experimental evidence demonstrated that the small-molecule inhibitor of BIRC5 (YM-155) synergistically sensitized ASXL1 deficient cells to decitabine treatment. This study sheds light on the molecular mechanisms underlying the ASXL1-associated HMA resistance and proposes a promising therapeutic strategy for improving treatment outcomes in affected individuals.

P1/2, N=32, Recruiting, Australasian Leukaemia and Lymphoma Group | Not yet recruiting --> Recruiting

P2/3, N=230, Active, not recruiting, Bristol-Myers Squibb | Recruiting --> Active, not recruiting

P2, N=11, Active, not recruiting, University of Florence | Recruiting --> Active, not recruiting | Trial completion date: Jul 2024 --> Dec 2024 | Trial primary completion date: Jul 2023 --> Aug 2024

Because the methods of determining maximum tolerated dose are not well suited to this paradigm, and because the mechanism of action, which is depletion of DNA methylase 1 (DNMT1), is complex and dependent on passing through a cell cycle, a pharmacodynamic assay that measures DNMT1 can inform clinical trials aimed at establishing and improving therapy. Herein, we provide an assay that measures DNMT1 relative levels in circulating T cells of peripheral blood.

P1, N=18, Recruiting, Astex Pharmaceuticals, Inc. | Phase classification: P1b --> P1

P1, N=27, Recruiting, Astex Pharmaceuticals, Inc. | Phase classification: P1b --> P1

P1, N=18, Recruiting, Pamela Munster | Not yet recruiting --> Recruiting

The objective of this study is to assess the anti-cancer efficacy of trichostatin C (TSC), an analogue of trichostatin A sourced from the fermentation of Streptomyces sp...When combined with the DNMT inhibitor decitabine, TSC exhibits a synergistic anti-cancer effect...In conclusion, our findings suggest TSC as a promising anti-cancer agent with HDAC inhibitory activity. Furthermore, our results highlight the potential utility of TSC in combination with DNMT inhibitors for cancer treatment.

Decitabine up-regulated RIPK3 expression and repaired endogenous R-2HG-induced necroptosis pathway in mIDH AML cells...The loss of RIPK3 protected mIDH AML cells from necroptosis. Restoring RIPK3 expression to exert R-2HG's intrinsic antileukemia effect will be a potential therapeutic strategy in patients with AML.

We conclude that early histological bone marrow examination for the development of an EDR may be helpful to predict response in AML patients during treatment with DAC.

This study reveals a novel mechanism underpinning self-renewal and tumor growth of CSLC (cancer stem cell) in NSCLC and identifies potential therapeutic targets for NSCLC treatment.

P=N/A, N=154, Recruiting, Bristol-Myers Squibb | Not yet recruiting --> Recruiting | Trial completion date: Sep 2029 --> May 2029 | Trial primary completion date: Jan 2028 --> Aug 2027

P1/2, N=36, Recruiting, Groupe Francophone des Myelodysplasies | Not yet recruiting --> Recruiting

Moreover, this bifunctional inhibitor induced the expression of endogenous retroviruses (ERVs) and elicited a viral mimicry response, which increased the intracellular levels of double-stranded RNA (dsRNA) to activate the innate immune signalling pathway in TNBC. In summary, we demonstrated that the bifunctional inhibitor J208, which is designed to inhibit HDAC and DNMT, has potent anticancer effects, providing a new research basis for reactivating antitumour immunity by triggering innate immune signalling and offering a promising strategy for TNBC treatment.

P1, N=30, Active, not recruiting, Otsuka Pharmaceutical Co., Ltd. | Trial completion date: Dec 2023 --> Jan 2026 | Trial primary completion date: Dec 2023 --> Jan 2026

Herein, a photo-responsive multifunctional nanosystem was designed for cancer therapy, in which myeloid-derived suppressor cell (MDSC) membrane vesicle encapsulated decitabine-loaded black phosphorous (BP) nanosheets (BP@ Decitabine @MDSCs, named BDM)...Flow cytometry revealed significantly decreased infiltration of MDSCs and M2-macrophages along with an increased proportion of CD4+, CD8+ T cells as well as CD103+ DCs, suggesting a potentiated anti-tumor immune response. In summary, BDM realizes photothermal therapy/photodynamic therapy synergized chemotherapy for cancer.

P2/3, N=422, Recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026 | Trial primary completion date: Mar 2025 --> Mar 2026

P4, N=12, Not yet recruiting, Virginia Commonwealth University

Biochemical and immunofluorescence results showed that βIV-spectrin inhibits DNMT1 function by activating ERK/MAPK, which in turn phosphorylates DNMT1 at S717 to impede its nuclear localization. Given that DNMT1 controls the DNA methylation patterns genome-wide, and is crucial for vascular development, our findings suggest that epigenetic regulation is a key mechanism by which βIV-spectrin suppresses angiogenesis.

Decitabine, a deoxyribonucleic acid (DNA) methyltransferase (DNMT) inhibitor, combined with cytarabine, aclarubicin hydrochloride, and granulocyte colony-stimulating factor (DCAG), has been used in patients newly diagnosed with AML. NGS demonstrated a dismal overall outcome in patients with the rare PTPN11 mutations, indicating the need for new therapies that target this high-risk subtype of AML. These results offer a potential molecular stratification and treatment guidance for patients with AML.

Enrichment of DNMT1 in FBXO32 promoter region led to increased DNA methylation and reduced transcription. Mechanistically, FBXO32 degraded CDK9 through promoting its ubiquitination.

In particular, mice bearing syngeneic 4T1 cancer showed higher tumor growth control when receiving the combinatorial treatment compared to single controls in association with a higher expression of MHC class I on cancer cells and reduction in Tregs within the tumor microenvironment. Furthermore, remodeling of the CD8+ T cell infiltration and cytotoxic activity toward cancer cells confirmed the effect of decitabine in enhancing anticancer vaccines in immunotherapy regimens.

P1, N=15, Not yet recruiting, Case Comprehensive Cancer Center

DNMT1 knockdown upregulated the expression of FOXO3a and E-cadherin, while downregulated N-cadherin expression in vivo. METTL3-mediated m6A methylation of DNMT1 up-regulates FOXO3a promoter methylation, thereby promoting the progression of NSCLC.

P=N/A, N=100, Recruiting, Centre Hospitalier Universitaire de Nice

P1/2, N=75, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

P1/2, N=188, Active, not recruiting, Astex Pharmaceuticals, Inc. | Recruiting --> Active, not recruiting

P1/2, N=132, Active, not recruiting, Astex Pharmaceuticals, Inc. | Recruiting --> Active, not recruiting

Analysis of primary human colon cancer specimens reveals positive correlations between DNMTi-, innate immune response-, and calcium signaling-associated transcription profiles. Collectively, we show that compensatory EZH2 activity limits DNMTi efficacy in colon cancer and link NFAT:AP-1 signaling to epigenetic therapy-induced viral mimicry.

P1, N=18, Recruiting, Massachusetts General Hospital | Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2022 --> May 2024

P1, N=14, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting | N=30 --> 14 | Trial completion date: Oct 2025 --> Mar 2025 | Trial primary completion date: Oct 2025 --> Mar 2024

P2, N=33, Active, not recruiting, Johns Hopkins University | Trial completion date: Nov 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Sep 2024

P2, N=20, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

P1, N=34, Completed, Kathy Miller | Recruiting --> Completed | Trial completion date: Jul 2025 --> Mar 2024 | Trial primary completion date: Dec 2024 --> Jan 2024

CAP combined with decitabine induced Caspase-3 activation, which cleaved decitabine-upregulated GSDME and ediated pyroptosis.

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

Our results suggest that the rs2228611 might be a potential biomarker for BC development risk. Additional studies are needed to validate our findings.

P1, N=12, Recruiting, OHSU Knight Cancer Institute | Trial completion date: Oct 2024 --> Jun 2025 | Trial primary completion date: Apr 2024 --> Dec 2024

P3, N=42, Recruiting, Otsuka Australia Pharmaceutical Pty Ltd | Not yet recruiting --> Recruiting | Phase classification: P3b --> P3

P3, N=86, Active, not recruiting, The Lymphoma Academic Research Organisation | Trial completion date: Feb 2024 --> Jun 2024

P2, N=21, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting