decitabine

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

P1, N=27, Not yet recruiting, Washington University School of Medicine

Gene expression and DNA methylation data from DAC-treated and untreated T-47D (Luminal-A) and JIMT-1 (HER2-amplified, trastuzumab-resistant with a TNBC-like phenotype) breast cancer cell lines were obtained from a published dataset. Survival analysis identified 114 DAC-responsive genes associated with overall survival in ER/PR-positive BC and 8 in the JIMT-1-derived gene set. DAC induces subtype-dependent epigenomic and transcriptional remodeling, selectively disrupts age-associated regulatory programs, and underscores the need for subtype-stratified evaluation of epigenetic therapies in breast cancer.

Before conditioning, 20 patients received intensive induction chemotherapy, 1 received decitabine plus venetoclax, and 3 proceeded directly to transplant. In conclusion, our results suggest that achieving remission before alloHSCT in BP-MF is associated with favorable outcomes. The adverse impact of TP53 or EZH2 mutations supports early post-transplant strategies to prevent relapse.

Navitoclax added to venetoclax/decitabine is safe and tolerable with preliminary activity in patients with high-risk myeloid malignancies.

Transferring the refined relationship matrix and learned weights to compound-induced perturbation data enables in silico drug screening, identifying BRD-K19103580 and decitabine as targeted therapeutic agents for apoptosis and ferroptosis, respectively. The pathway-resolved drug profiles can facilitate the rational design of combination therapies targeting complementary PCD pathways to overcome single-pathway resistance. Overall, xNNPCD offers a generalizable, interpretable approach for mapping the regulatory landscape and elucidating the molecular processes of PCD in cancer.

Decitabine effectively inhibits malignant progression of OPMDs without apparent toxicity, potentially through SOX1 demethylation and subsequent Wnt pathway regulation, suggesting promising clinical value in preventing malignant transformation of OPMDs.

In addition, high-risk patients exhibited significant enrichment in pathways related to TP53 dysfunction, mechanistic target of rapamycin complex 1 (mTORC1) signaling activation, and pro-inflammatory responses, which were closely correlated with NPM1c-FLT3 co-mutations. Decitabine, sunitinib, and MK-1775 were identified as potential therapeutic agents. In summary, we established a 5-ARG prognostic model that may facilitate risk stratification and inform therapeutic decision-making in AML.

P1, N=6, Completed, Thomas Jefferson University | Active, not recruiting --> Completed

We demonstrated prolonged survival, particularly in patients with IDH mutations, using the modified intervention. This approach holds significant value for elderly patients with untreated AML who are unfit for standard treatments.

P2, N=178, Not yet recruiting, Ruijin Hospital