decitabine

P2, N=46, Active, not recruiting, Virginia Commonwealth University | Trial completion date: Mar 2026 --> Mar 2027

P1, N=17, Active, not recruiting, City of Hope Medical Center | Trial completion date: Apr 2026 --> Mar 2027 | Trial primary completion date: Apr 2026 --> Mar 2027

Previously, we showed that ex vivo priming with decitabine (DAC) enhances CAR T persistence and efficacy. Single-cell sequencing indicates that DAC priming enriches for memory-like progenitors, which maintain cytotoxic and memory signatures, and upregulates genes associated with T cell fitness and engagement of endogenous immunity. These data establish DAC-priming as a clinically feasible epigenetic reprogramming strategy enhanceing CAR T durability and efficacy, offering a generalizable paradigm for engineered cell therapies in malignant tumors.

Decitabine was predicted as a potential agent targeting these genes, with DUSP13 showing strong binding affinity (-6.9 kcal/mol)...Their expression patterns may provide supplementary molecular evidence to support the early identification and dynamic risk monitoring of high-risk patients. However, the clinical translational potential of these findings requires further validation through large-scale, multicenter prospective studies.

Age, bone marrow blasts, iron overload, and high-risk cytogenetics are key prognostic factors. Incorporating clinical, cytogenetic, and mutational variables into new prognostic models may enhance individualized treatment decision-making for high-risk MDS patients.

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.