FANCA mutations in four patients were linked to a higher relapse risk (HR = 4.96, p = 0.02) for DFS at both 2 and 5 years. Further HLA-specific NGS analyses are ongoing to confirm these results and their therapeutic implications.

Cells were treated with demethylating 5-azacytidine and pyrosequencing was performed...In summary, combination miR-100-5p/miR-125b-5p mimic replenishment or TRIM71kd caused growth inhibition in malignant GCT cells via cell cycle disruption. Further studies are now warranted, including mimic treatment alongside conventional platinum-based chemotherapy.

In conclusion, 4‑MD may exhibit anticancer activity through the promotion of DNMT1‑mediated cell ferroptosis. Thus, 4‑MD may have potential as a novel therapeutic agent in the treatment of lung cancer.

This upregulation, in turn, enhanced the cells' sensitivity to HER2 antagonists, indicating that DI-1's mechanism involves inhibiting DNMT-1's recruitment to PTEN's promoter region. Consequently, by increasing PTEN expression, DI-1 amplifies the sensitivity of HER2-positive breast cancer cells to treatment, suggesting its potential as a promising therapeutic strategy in this context.

P1, N=8, Active, not recruiting, Roswell Park Cancer Institute | Recruiting --> Active, not recruiting | N=18 --> 8 | Trial completion date: Jan 2025 --> Mar 2026

P4, N=12, Recruiting, Virginia Commonwealth University | Not yet recruiting --> Recruiting

P=N/A, N=76, Recruiting, Ningbo First Hospital; Ningbo First Hospital

P1, N=20, Recruiting, Benjamin Tomlinson | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

Background: Venetoclax (ven) with azacitidine (aza) is the standard of care for newly diagnosed AML patients who are unfit for intensive induction chemotherapy. CC-486 (oral azacitidine) and ven is an all-oral regimen currently being investigated for the treatment of ND and R/R AML. The phase I portion of this study previously showed the MTD of CC-486 with ven to be 300mg d1-14 (Amaya et al. 2023).

Overall, our findings shed light on the intricate interactions between TET1, Wnt1, and specific miRNAs in colorectal cancer (CRC) and their potential implications for diagnosis and treatment.

Additionally, the transcriptomes of these cells were reprogrammed to become highly responsive to chemotherapy (cisplatin), targeted therapy (trametinib), and epigenetic therapy (vorinostat). SCARA5 and AOX1 DNA promoters were hypermethylated in NSCLC, and SCARA5 methylation was identified as an epigenetic biomarker in tumors and liquid biopsies from NSCLC patients. Thus, we demonstrate that co-targeting G9a/DNMT1 is a promising strategy to enhance the efficacy of cancer drugs, and SCARA5 methylation could serve as a non-invasive biomarker to monitor tumor progression.

The response to AZA was positively associated with the enrichment of IFN-mediated pathways, whereas an enhanced TGF-β signaling signature was observed in non-responders. Our results suggest that targeting CD8+ T cells with inhibitors of TGF-β signaling in combination with AZA is a potential therapeutic strategy for HR-MDS and AML.

P2/3, N=317, Active, not recruiting, Taiho Oncology, Inc. | Recruiting --> Active, not recruiting

SYNE1 contributes to the modulation of sorafenib resistance in ccRCC cells through interacting with BIN1. Decitabine treatment enhances expressions of these two proteins to improve TKI response, suggesting a potential strategy for counteracting resistance and bettering patient outcomes.

P1/2, N=55, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2024 --> Oct 2025 | Trial primary completion date: Aug 2024 --> Oct 2025

Herein, an injectable hydrogel-encapsulated autocatalytic copper peroxide (CP@Gel) therapeutic platform is designed and combine it with the clinical-grade DNA methyltransferase inhibitor decitabine (DAC) to effectively inhibit TNBC growth and postoperative recurrence via pyroptosis, killing residual cancer cells that bypass apoptosis resistance while also improving immunogenicity and modulating immunosuppression to achieve an intense anti-tumor immune response...The in vivo results show a 67% elimination of local tumor recurrence via treatment with DAC+CP@Gel, suggesting the successful integration of sustained drug release with autocatalysis and epigenetic modification. The results thus suggest great potential for pyroptosis-based and injectable hydrogel-aided strategies for preventing the postoperative recurrence of TNBC.

P1/2, N=0, Withdrawn, M.D. Anderson Cancer Center | N=36 --> 0 | Initiation date: Jul 2024 --> Jan 2025 | Not yet recruiting --> Withdrawn

This data suggests that DNMT inhibitors cause changes in UM cells that are maintained in cfDNA. The results suggest that targeting methylation in UM treatment and monitoring response to treatment using cfDNA methylation could be a valuable tool.

Objective: To investigate the efficacy and prognosis of CLAG±DAC (Clofarabine, Cytarabine, G-CSF±Decitabine) chemotherapy in patients with relapsed/refractory acute myeloid leukemia (R/R AML) . The remission rate was relatively higher in patients with R/R AML combined with FLT3-ITD mutation by applying the DAC+CLAG regimen (OR=10.84, 95%CI 1.48-288.50, P=0.04) . The CLAG±DAC regimen is considered effective in patients with R/R AML, whereas decitabine combined with the CLAG regimen is more suitable for patients with R/R AML combined with FLT3-ITD mutation.

Furthermore, DAC + DOX@FPSD NP treatment could promote pyroptosis-associated antitumor immunity, as evidenced by the increased presence of CD3+, CD4+, and CD8+ T cells, heightened secretion of tumor necrosis factor-α and interferon-γ, elevated high-mobility group box-1 levels, and enhanced calreticulin exposure. The FPSD nanocarrier developed in this study had favorable stability, active targeting ability, biocompatibility, and controlled release properties, and the DAC + DOX@FPSD NPs represented an approach to antitumor therapy by inducing pyroptosis, which offers a promising avenue for breast cancer treatment.

To demonstrate the role of DNA methylation in this response process, BMMCs that recognize FMDV-VLPs were treated with azacytidine (5-AZA), an inhibitor of DNA methylation transferase...All the data demonstrate that DNA methylation negatively regulates the transcription and expression of TNF-α, IL-13, IL-10, and IL-6 secreted by recognizing FMDV-VLPs. These results provide new ideas for the mast cell-based design of more effective vaccine adjuvants and targeted therapies in the future.

P=N/A, N=154, Recruiting, Bristol-Myers Squibb | Trial completion date: May 2029 --> Jul 2027

P2, N=55, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed

Our findings advanced the mechanistic understanding of variations in PER3 expression in cancers and confirmed the tumor-associated function of PER3 hypermethylation and downregulation.

In a randomized phase II trial (AMLSG 14-09, NCT00867672) of elderly, newly diagnosed AML patients, ATRA combined with decitabine (DEC) significantly improved the overall response rate (ORR) and survival also in patients with adverse-risk genetics, without adding toxicity. Further studies of ATRA combined with hypomethylating agents appear warranted in non-M3 AML patients ineligible for HMA/venetoclax therapy. Trial Registration: ClinicalTrials.gov identifier: NCT00867672.

Intravenous administration of these NPs significantly suppressed tumor growth in HNSCC animal models and enhanced the antitumor immune response. The NIR-controlled activation of cuproptosis offers great potential as a safe, targeted, and image-guided antitumor therapy for HNSCC.

P1, N=40, Recruiting, GlaxoSmithKline | Trial completion date: Mar 2025 --> Sep 2025 | Trial primary completion date: Mar 2025 --> Sep 2025

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

P1, N=40, Recruiting, Otsuka Pharmaceutical Co., Ltd. | Trial completion date: Dec 2024 --> May 2025 | Trial primary completion date: Nov 2024 --> Apr 2025

P2, N=2, Terminated, Astex Pharmaceuticals, Inc. | N=100 --> 2

P2, N=78, Active, not recruiting, Bristol-Myers Squibb | Recruiting --> Active, not recruiting

The small molecular probe has certain application value in differentiating the type of cervical lesions and has better efficacy in distinguishing cervical inflammatory and precancerous lesions from carcinogenesis, but less efficacy in determining the type of precancerous lesions.

Future research should incorporate larger sample sizes and advanced genomic techniques like RNA sequencing to better understand oncogenic mechanisms. The study emphasizes the need for further in situ analyses of decitabine's efficacy, setting the foundation for future neuro-oncological treatments.

Next-generation sequencing was performed to identify molecular abnormalities that impact OS and TP53 mutations were associated with a poor outcome. These findings support the use of oral DEC-C in patients with AML.

The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

SLNCR1 is an oncogene that interacts with DNMT1 to mediate SPRY2 methylation, thereby suppressing SPRY2 expression and promoting the angiogenesis and tumor growth in melanoma. SLNCR1 may serve as a potential target for melanoma treatment.

In conclusion, these findings proved the capability of PROTAC strategy for inducing DNMT1 degradation, demonstrated the therapeutic potential of DNMT1-targeted PROTACs. This work also provided a convenient chemical knockdown tool for DNMT1-related studies.

No abstract available

P1, N=8, Active, not recruiting, Joseph Tuscano | Trial completion date: Dec 2024 --> Jul 2025 | Trial primary completion date: Apr 2024 --> Dec 2024

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

P2, N=100, Recruiting, M.D. Anderson Cancer Center | N=40 --> 100 | Trial completion date: Oct 2024 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Oct 2026

P1/2, N=43, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026