decitabine

SNS-032 is a synthetic compound that specifically inhibits cyclin-dependent kinases 2, 7 and 9. In conclusion, these results suggest that caspase-3/GSDME-induced pyroptosis can be facilitated by SNS-032 treatment in BC cells, and DAC has the potential to enhance SNS-032-induced pyroptosis by increasing GSDME expression. This mechanistic insight indicates that SNS-032 is a promising therapeutic agent for BC treatment.

P1, N=48, Recruiting, Bio-Path Holdings, Inc. | Trial completion date: Sep 2024 --> Sep 2027 | Trial primary completion date: Mar 2024 --> Mar 2027

P2, N=108, Recruiting, Bio-Path Holdings, Inc. | Phase classification: P2a --> P2 | Trial completion date: Dec 2024 --> Dec 2028 | Trial primary completion date: Dec 2024 --> Dec 2027

P1, N=35, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting --> Recruiting | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Jun 2025 --> Jan 2026

P3, N=450, Recruiting, Delta-Fly Pharma, Inc. | Trial primary completion date: Dec 2022 --> Dec 2025 | Trial completion date: Dec 2022 --> Jun 2026

Treatment in the pre-neoadjuvant window with decitabine and pembrolizumab could sensitize breast cancers to standard NCT by recruitment of TILs to the tumor tissue. The treatment was well-tolerated.

P2, N=33, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Nov 2025 --> Feb 2028 | Trial primary completion date: Nov 2025 --> Feb 2028

In summary, selinexor in combination with decitabine has significant synergistic effects both in vitro and in vivo and represents a new treatment option for RR T-LBL.

We found a critical role of KIAA1199 in promoting immunotherapy resistance by suppressing pyroptosis via the DNMT1/GSDME pathway in CRC. Decitabine has emerged as a promising therapeutic agent for reversing KIAA1199-mediated immunotherapy resistance by enhancing pyroptosis. Our findings provide valuable insights for enhancing the efficacy of immunotherapy in patients with CRC who exhibit resistance to conventional immunotherapy approaches.

Patients aged 18-59 years eligible for intensive chemotherapy were randomized 1:1 to receive VEN-DEC or IA-12 (idarubicin and cytarabine). In conclusion, VEN-DEC demonstrated non-inferior response rates with superior safety over IA-12 in young AML patients. The trial was registered at ClinicalTrials.gov as #NCT05177731.

The combination was especially effective in dKRAS-PDAC with a BRCA2 mutation, preventing metastasis growth. Our results support the clinical evaluation of DEC+OLA in PDAC.

P1/2, N=218, Active, not recruiting, AbbVie | Trial completion date: Apr 2026 --> Feb 2027 | Trial primary completion date: Apr 2026 --> Feb 2027

Our findings suggest that the dual-targeting of DNMT and TET enzymes effectively repairs aberrant DNA methylation and induces growth arrest in cancer cells, and the dual-targeting strategy may contribute to the advancement of epigenetic cancer therapy.

P2, N=66, Recruiting, The First Affiliated Hospital of Xiamen University

To enhance this combined therapy, the DNA methyltransferase inhibitor decitabine (DAC) was used to increase Gasdermin E (GSDME) expression, converting apoptosis to pyroptosis. This approach kills apoptosis-resistant tumor cells, and also promotes T cell infiltration and activation, facilitating an anti-PDL1 therapy and the systemic antitumor immune response. This multifaceted therapeutic strategy combines gene therapy with epigenetic regulation to significantly improve immune checkpoint therapy (ICT) effectiveness, offering a robust potential as a transformative cancer treatment.

P2, N=33, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=70 --> 33 | Trial completion date: Feb 2028 --> Nov 2025 | Trial primary completion date: Feb 2028 --> Nov 2025

No abstract available

P2, N=37, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Jun 2028 --> Aug 2026

P1/2, N=6, Active, not recruiting, Thomas Jefferson University | Trial completion date: Jul 2025 --> Apr 2026 | Trial primary completion date: Jan 2025 --> Apr 2026

By exploring candidates for synthetic lethality, we unexpectedly uncover that KDM1A promotes survival after DAC treatment through interactions with ZMYM3 and CoREST, independent of its demethylase activity or regulation of viral mimicry. These findings emphasize the importance of DNA repair pathways in DAC response and provide potential biomarkers.

No abstract available

P1, N=17, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2025 --> Mar 2025

P1, N=22, Not yet recruiting, M.D. Anderson Cancer Center | Initiation date: Dec 2024 --> Dec 2025

P2, N=152, Not yet recruiting, Ruijin Hospital

Our study first shows that DNA methylation-mediated suppresser role of PRDM16 in CRC progression via PPAR γ/EMT pathway.

P1, N=9, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=45, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

P1, N=16, Active, not recruiting, Jacqueline Garcia, MD | Trial primary completion date: Dec 2024 --> Dec 2025

Treating TAMR cell with Decitabine, a demethylating agent, or Farudodstat, a pyrimidine biosynthesis inhibitor, markedly augmented efficacy of tamoxifen. Restoring ASS1 expression or inhibiting pyrimidine biosynthesis restored tamoxifen sensitivity. ASS1 could be a potential biomarker and therapeutic target in tamoxifen resistant ILC patients, warranting further investigation.

To elucidate how epigenetic dysregulation alters the expression of surface proteins that may be involved in drug targeting and immune escape, we performed a 3-dimensional surfaceome screen in primary melanoma cultures and identified the DNA-methyltransferase inhibitor decitabine as significantly upregulating the costimulatory molecule ICAM-1...Our in silico analysis on The Cancer Genome Atlas and ex vivo experiments on human primary melanoma samples revealed that increased ICAM-1 expression positively correlated with increased immunogenicity of human melanoma cells and correlated with increased immune cell infiltration. These findings suggest a therapeutic approach to modulate the immunogenic phenotype of melanoma cells, hence supporting the exploration of DNA-methyltransferase inhibitor as a potential inducer of infiltration in immunologically cold tumors.

P1/2, N=33, Active, not recruiting, Beth Israel Deaconess Medical Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

P1, N=45, Recruiting, Beth Israel Deaconess Medical Center | Trial primary completion date: Aug 2024 --> Aug 2025

P1, N=12, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P4, N=43, The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Soochow University

P1, N=18, The First Affiliated Hospital of Xiamen University; The First Affiliated Hospital of Xiamen University

We conclude that low dose DNA methyltransferase inhibition can cooperate with low dose PARP inhibition to increase DNA damage predominantly in cells with HRR deficiencies, ultimately producing more cell death than in HRR proficient tumors. We predict that clinical benefit will more likely be apparent in patients with DNA repair defective tumors and are focusing clinical exploration of this drug combination in these patients, with the goals of enhancing tumor cell death at minimal toxicities.

Treatment included intensive chemotherapy (IC) (36.8%), Low-Intensity Regimen Based on Low-Dose Cytarabine (LDAC-based) (12.6%), hypomethylating agents (HMAs, with/without venetoclax) (35.3%), and supportive care (15.2%). The overall survival (OS) rate was 35.2% at 1 year and 5.6% at 5 years (13.7% for IC, 9.4% for LDAC-based, and 0% for other treatments); with median OS of 8.2 months (10.6 months after IC, 8.8 months after non-IC, 8.9 months after azacitidine/decitabine, 8.2 months after azacitidine-venetoclax, and 1.9 months with supportive care)...The Leukemia-free survival (LFS) rate was 45.8% at 1-year and 13.7% at 5-years (22.4% for IC, 9.4% and 0% for other treatments); with median LFS of 9.5 months (17.3 months after IC, 7.4 months after LDAC-based, and 10.8 months after HMA). This study provides new insights into the management of patients in Colombia, highlighting the need for a highly individualized approach in treating AML in elderly patients.

P2/3, N=76, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Oct 2025 --> Jun 2024

P1/2, N=64, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026

The results of molecular docking showed that the predicted drugs can bind well to the core targets. In conclusion, cadmium is associated with NAFLD; the identified cadmium-toxicity targets, HCK, MYC, and DUSP6, may serve as biomarkers for the diagnosis of NAFLD and predicted drugs, decitabine and retinoic acid may have a potential role in the treatment of NAFLD.

P2, N=100, Active, not recruiting, Gruppo Italiano Trapianto di Midollo Osseo | Completed --> Active, not recruiting | Trial completion date: Dec 2022 --> Jun 2025

P1, N=30, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Dec 2024 --> May 2025