decitabine

P1, N=32, Not yet recruiting, Northside Hospital, Inc.

Decitabine restores gasdermin E expression to couple oxidative stress with caspase-3-mediated pyroptosis, while chlorogenic acid repolarizes tumor-associated macrophages toward a pro-inflammatory phenotype. This coordinated multimodal cell-death cascade establishes a self-amplifying immunogenic circuit that suppresses tumor growth, sensitizes CRC to ICB, and elicits systemic antitumor immunity.

P1/2, N=33, Completed, Beth Israel Deaconess Medical Center | Active, not recruiting --> Completed

Therapeutic strategies including activation of NK cells via chemotherapeutics (bortezomib, decitabine), blockade of inhibitory receptors (NKG2A, CD161), and combinatorial approaches with immune checkpoint inhibitors are under active investigation. Notably, chimeric antigen receptor (CAR)-engineered NK cells targeting EGFR, HER2, GD2, and CD133 show promise in preclinical glioma models due to their enhanced specificity and reduced toxicity compared to CAR-T cells. This review summarizes the multifaceted roles of NK cells in glioma immunity and highlights novel immunotherapeutic strategies to restore NK cell function and improve clinical outcomes.

Venetoclax (Ven) in combination with hypomethylating agents (HMA) (azacitidine or decitabine) is the standard of care for elderly or unfit patients with acute myeloid leukemia (AML) and is being explored in high-risk myelodysplastic syndrome (HR-MDS). Neutropenic fever occurred in 15%, there were no therapy-related fatalities, and the 100-day mortality was 7.5%. A non-cytotoxic metronomic dosing schedule of decitabine/Ven has a low toxicity profile in TP53-mutated myeloid malignancies.

P2, N=35, Not yet recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

Decitabine and GSK3685032 reduced histone lysine acetylation and methylated-lysines whereas GSK3685032 had minimal effects on histone modifications in cells. Our results suggest that some doses of DNMT inhibitors may increase p16 expression making them potentially effective in gastric cancer, while higher doses will decrease p16 expression possibly reducing efficacy.

Among the three patients who received at least three cycles of decitabine, improvements in anemia and thrombocytopenia were observed in those with elevated NKT-like cell levels. These findings suggest that low-dose decitabine may enhance the NKT-like cell population, which may be associated with therapeutic responses in chronic myeloid neoplasms.

Furthermore, BIS-LNPs@DCA-siTNF attenuated osteoclastogenesis, restored bone integrity, and improved locomotor performance. These results establish BIS-LNPs@DCA-siTNF as a programmable nanoplatform that overcomes both pharmacological and microenvironmental barriers, offering a promising approach for enhanced AML therapy.

Hypomethylating agents (HMAs) such as azacitidine and decitabine can reverse abnormal DNA methylation, promote leukemic cell differentiation, and enhance immune recognition, yet relapse and therapeutic resistance remain major challenges. In multiple xenograft models, AlloCAR70-NKT cells effectively killed AML tumors without inducing graft-versus-host disease, cytokine release syndrome, or long-term organ toxicity. These findings highlight AlloCAR70-NKT cells as a safe and powerful off-the-shelf immunotherapy that can synergize with HMAs to improve treatment outcomes for patients with AML.

P1/2, N=86, Not yet recruiting, Ruijin Hospital

The combined treatment was associated with downregulation of DNMT1, a reduced Bcl‑2/Bax ratio, and upregulation of HOXA9, p21, and E‑cadherin. These preclinical findings suggest that the combination of BS and DAC represents a mechanistically rationalized and promising therapeutic strategy for lung cancer that warrants further evaluation in in vivo models and early‑phase clinical trials.