CREBBP (CREB binding protein)

Definitive diagnosis relies on molecular testing (such as FISH or NGS), which is crucial for differential diagnosis and prognostic evaluation. This subtype of CCSK is commonly associated with advanced clinical stage and early metastasis/recurrence, highlighting the necessity for improving risk stratification and clinical management.

Molecular docking and molecular dynamics simulations confirmed the strong affinity of cypermethrin for CREBBP, GSK3B, and ALB. These findings provide a foundation for the development of diagnostic tools for diseases linked to cypermethrin exposure, although further experimental and clinical validation is necessary.

Enhanced Prmt7-dependent tumor growth was not observed in immunodeficient mice, implicating Prmt7 in immune evasion. This study underscores the utility of CRISPR screens for high-throughput functional follow-up of GWAS findings and identifies PRMT7 inhibition as a promising therapeutic strategy.

TP53/RB1 co-alterations define an aggressive cancer subset with dysregulated cell cycle/chromatin pathways and reduced immunotherapy response. Targeting CDK, AURKA, or PI3K signaling offers promising therapeutic strategies.

GSCC is a highly malignant tumor with a poor prognosis. Whether immune-related drugs are optimal for metastatic GSCC requires further exploration.

In the in vivo orthotopic xenograft osimertinib-resistant models, targeted suppression of the tumor-derived lactate/ENO1 lactylation feedback loop effectively ameliorated resistance to osimertinib. Collectively, our findings provide the basis for targeting lactate/lactate-associated signaling to combat resistance to osimertinib.

We showed that several stapled sulfonyl-γ-AApeptides could suppress CREB-mediated gene transcription and exhibit effective antiproliferative activity in cell-based assays and demonstrate its potency in inhibiting tumor growth in vivo. Our studies suggest that sulfonyl-γ-AApeptides as a class of helical foldamer could mimic the helical kinase-inducible activation domain of CREB (KID) to target the hydrophobic grooves on the surface of CBP KIX domain, and thereby inhibiting KIX-KID interaction, which provides a new strategy for the development of antitumor agent by targeting PPIs involving intrinsically disordered proteins (IDPs).

Compared to CCS1477, it shows comparable in vivo efficacy in the OPM-2 xenograft model and demonstrates more potent antitumor activity in the 22RV1 xenograft model, with tumor growth inhibition values of 56.2% and 72.8%, respectively. Overall, CZL-077 is a promising candidate for the treatment of human cancer as a p300/CBP BRD inhibitor.

Therapeutic targeting of H3K27me3 with EZH2-selective inhibitors such as tazemetostat has shown clinical benefit in lymphoma; however, their efficacy is limited by functional redundancy with EZH1. The dual EZH1/2 inhibitor valemetostat overcomes this limitation by reactivating tumor suppressor genes, achieving durable responses in ATL and peripheral T-cell lymphoma (PTCL). Nonetheless, therapeutic resistance can emerge through PRC2 gatekeeper mutations and compensatory DNA methylation. These findings underscore the value of targeting the dysregulated epigenome and support the continued clinical development of dual EZH1/2 inhibitors.

This suggests that similar differentiation processes may contribute to tumor heterogeneity in patients. This study presents the model system enabling reversible switching between a transformed and differentiated cell state in a human cancer using small-molecule treatment.

This study, integrating computational analysis, including network target and bioinformatics, with cellular experimental validation, reveals the inhibitory potential of PZH on hepatocellular carcinoma progression through the regulation of cell cycle-related pathways and biological processes. Notably, this study provides the first mechanistic insight into how PZH intervenes in the multi-step hepatocarcinogenesis, highlighting its potential role in preventing liver cancer development.

We showed that this peptide variant binds with a stronger affinity to its target proteins than the wild-type peptide and inhibits CBP/p300 acetylase activity. This peptide variant also modulates interactomes and CBP/p300-mediated gene transcription and exhibits effective antiproliferative activity in cell-based assays.