Notably, Napabucasin effectively inhibited ovarian cancer metastasis in vivo. Collectively, our findings elucidate a previously unrecognized mechanism by which EZH2 governs metastatic progression through cholesterol metabolic rewiring and propose Napabucasin as a promising therapeutic strategy for ovarian cancer, particularly in tumors with EZH2 hyperactivation.

Our findings revealed a signalling pathway in which lung adenocarcinoma regulates stemness and tumourigenesis through HES1, and the targeting of this pathway by VR23 or napabucasin supports further preclinical development for CDK4/6 inhibitor combination therapy.

Notably, SHN7 exerted strong in vivo anti-tumor effects relative to napabucasin and SAHA, with minimal toxic effects. Therefore, SHN7 may be a promising NQO1/STAT3/HDAC triple-target agent that can decrease the resistance of TNBC to HDAC inhibitors and can be developed as a candidate anti-TNBC drug.

P1/2, N=29, Active, not recruiting, University of Colorado, Denver | Trial primary completion date: Feb 2030 --> Jun 2026

The prepared NCM-ERL-Liposomes showed enhanced internalization, triggered caspase-3/7-mediated apoptosis (1.42-fold increase), and suppressed p-EGFR/p-STAT3, indicating adequate payload protection and targeted intracellular release. These results establish a translational platform that requires PK/PD studies in resistant NSCLC models to support precision oncology therapeutics.

Notably, 7-methoxyheptaphylline markedly suppressed STAT3 phosphorylation in a concentration-dependent manner, comparable to the STAT3 inhibitor JSI-124...Collectively, our results demonstrate that C. harmandiana exerts broad-spectrum anticancer activity through coordinated modulation of the JNK-STAT3 axis, leading to caspase-dependent apoptosis. These findings highlight its potential as a promising candidate for the development of STAT3-targeted anticancer therapies.

P1/2, N=48, Active, not recruiting, Accendatech USA Inc. | Recruiting --> Active, not recruiting | Phase classification: P1b/2a --> P1/2 | Trial completion date: Nov 2023 --> Dec 2026

Subsequent in vitro experiments demonstrated that CuI treatment upregulated SDHA expression and inhibited activation of the NF-κB pathway. Collectively, these findings suggest that the identified PBs may serve as early-warning indicators for stage I COAD patients and that CuI suppresses COAD cell proliferation, potentially through the SDHA/NF-κB axis, highlighting its promise as a potential therapeutic candidate.

These modified compounds can be tested to determine which are most effective on cancer treatment. These findings are important in the development of multi-functionalized niclosamide and drug design therapy in the future.

Furthermore, it reduced the p-STAT3/STAT3 ratio and decreased PD-L1 and c-Myc expression in tumor tissues. SS exerts potent anti-NSCLC effects by blocking the STAT3/PD-L1 signaling pathway and suppressing EMT, suggesting its potential as a therapeutic agent for NSCLC.

These effects were effectively reversed by the stemness inhibitor Napabucasin...In summary, this study reveals that PMN-MDSCs can activate the STAT3-CXCL5-ERK positive feedback regulatory axis via exosomal S100A9, synergistically enhancing breast cancer cell stemness and metastatic capacity. These findings provide a theoretical reference and potential intervention targets for targeting the tumor microenvironment to inhibit TNBC progression.

Moreover, we identified ACT001 as a novel USP22 inhibitor, and ACT001 induced substantial ERK1/2 ubiquitination and its subsequent degradation, efficiently suppressing the growth of CRC cells in vitro and in vivo by targeting USP22. Overall, this study revealed the mechanism underlying the role of hyperregulated ERK1/2 in CRC development, providing further insights into the pathology of CRC and the potential applicability of USP22-ERK1/2 as a therapeutic target in CRC.