decitabine

Therapeutically, combinatorial targeting of MTHFD2 with its selective inhibitor and the hypomethylating agent decitabine induced ferroptosis in patient-derived IDH-mut glioma organoids, demonstrating potent ferroptosis activation. This work delineates an RNA epitranscriptomic-metabolism axis in glioma pathogenesis and provides a translational roadmap for exploiting metabolic dependencies in IDH-driven malignancies. CLINICAL TRIAL NUMBER: Not applicable.

Treatment of human sarcoma lines with decitabine and entinostat induced similar gene expression changes, including shared antigen targets, and increased MHC I expression. These findings demonstrate that epigenetically upregulated antigens can serve as effective tumor-specific targets and broaden immunotherapy strategies for low-mutation sarcomas.

An 8-year-old female patient achieved bone marrow remission with azacitidine and venetoclax and subsequently underwent allogeneic hematopoietic stem cell transplantation from an unrelated umbilical cord blood donor, The conditioning regimen included fludarabine, decitabine, busulfan, and cyclophosphamide, leading to sustained donor engraftment. At the 13-month follow-up, the patient remained in complete hematologic remission without recurrence. This case suggests that allo-HSCT is a feasible curative option for children with high-risk MDS and germline DDX41 predisposition, highlighting the critical importance of screening potential donors for the same mutation.

P1, N=0, Withdrawn, Case Comprehensive Cancer Center | N=15 --> 0 | Not yet recruiting --> Withdrawn

We show that the treatment with cAzadC goes in hand with the broad reactivation of the cellular antitumor responses. With patient-derived xenograft AML-mouse models, we show that this translates into a strongly improved anticancer effect in vivo.

Overexpression of anti-apoptotic protein BCL-2 and hypermethylation are hallmarks of acute lymphoblastic leukemia (ALL) and can be pharmacologically addressed by venetoclax (VEN) and hypomethylating agents (HMA) such as azacytidine (AZA) or decitabine (DEC). AZA-induced metabolic suppression as well as overall anti-leukemic activity alone and in combination with VEN was generally weaker compared to DEC. Altogether, we herein demonstrate that combined VEN and HMA application acts synergistically and significantly reduces the leukemic burden in ALL cell lines via impairment of tumor cell metabolism and mitochondrial function.

Based on treatment regimens, the patients were categorized into chemotherapy group ("3+7"regimen), demethylation therapy (HMA) group (decitabine-based therapy), and UCB group (venetoclax combined with azacitidine plus UCB reinfusion). Cytokine level analysis demonstrated that the direct co-culture group showed higher levels of TNF-α and IFN-γ, as well as lower levels of IL-6 compared to the control group (P<0.001). Immunocytes such as NK cells in UCB may promote immune function reconstruction and hematopoietic recovery in patients, thereby improving their prognosis.

While currently, hypomethylating agent therapy (azacitidine and decitabine) is mainly used in high-risk MDS patients, and ruxolitinib is primarily used in symptomatic primary myelofibrosis (PMF-MPN), their clinical efficacy remains suboptimal. In response, a new generation of immune checkpoint inhibitors are being developed to target the TME, including PD-1/CTLA-4 blockers, macrophage-directed agents including CD47 inhibitors, and T cell-targeting checkpoint inhibitors such as TIM-1 and LAG-3. This review will describe the functional role of key TME constituents in the progression of myeloid malignancies and explore the current landscape and future potential of advanced cellular and molecular immunotherapies in the treatment of these disorders.

P1, N=58, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Jun 2026 --> Jun 2027

Mechanistic investigations uncovered that the tumor-suppressive effect of APCDD1 was mediated by promoter hypermethylation, and its expression could be restored by the demethylating agent Decitabine. We further propose Leflunomide as a novel therapeutic strategy for high-risk WT patients. These findings advance our understanding of WT biology and provide actionable insights for risk stratification and targeted intervention.

Here, we define a clinically actionable strategy that functionally targets PLK1 by combining inhibition of the AAA+ ATPase p97/valosin-containing protein (VCP) with the hypomethylating agent decitabine (DAC). In vivo, CB-5339/DAC is well tolerated, significantly prolongs survival, reduces leukemic burden, and suppresses PLK1 in bone marrow blasts. Together, these data establish p97 inhibition as a rational means to exploit replication and proteotoxic stress in AML and provide strong rationale for clinical evaluation of CB-5339 plus DAC in high-risk disease.

P2, N=20, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Nov 2026 --> Jun 2026 | Trial primary completion date: Nov 2026 --> Jun 2026