P4, N=100, Not yet recruiting, Tongji Hospital

Pharmacological inhibition of the TNF signaling pathway with R-7050 completely abolished the synergistic efficacy of RT/TMZ/ACT001. Taken together, our results demonstrate that ACT001 combined with RT/TMZ can overcome the immunosuppressive barrier of GBM to achieve immune cure in GBM via TNF-CXCL10-CD8+ signaling, strongly suggesting the priority of combining ACT001 with RT/TMZ rather than with αPD-1 in clinical trials.

Importantly, either the knockdown of MDM4 or pharmacological inhibition of JAK2/STAT3 signaling pathway with JSI-124 partially attenuated MTX-induced ferroptosis, improved renal function indicators, and attenuated histopathological damage in vivo. Our findings demonstrate that MTX mediates phosphorylation-dependent activation of the JAK2/STAT3 pathway, which facilitates MDM4/MDM2 interaction to induce ferroptosis-associated nephrotoxicity. These findings support a role for JAK2/STAT3-MDM4/MDM2 signaling in MTX-induced ferroptosis and suggest that targeted inhibition of this axis may represent a potential nephroprotective strategy.

P1/2, N=32, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

P2, N=69, Terminated, Flamingo Therapeutics NV | Trial completion date: May 2026 --> Aug 2025 | Recruiting --> Terminated; Interim analysis was negative

P4, N=58, Not yet recruiting, Zhongshan hospital, Fudan University; Zhongshan hospital, Fudan University

This study reveals the critical role of FUBP3 in lung cancer metastasis and identifies a new regulatory axis involving FUBP3-STAT3-Twist1. FUBP3 interacts with STAT3, enhancing STAT3-dependent Twist1 expression, which promotes EMT and metastasis. FUBP3 functions as a prognostic biomarker, and STAT3 inhibitors present therapeutic strategies for lung cancer, offering novel insights for precision treatment.

Canonical NF-κB signaling is mechanistically related to UM cell survival, proliferation, and migration, as shown by pharmacologic inhibition like BAY11-7082, and niclosamide and genetic modulation like microRNA-9. NF-κB signaling, particularly the canonical branch, is required for UM malignancy, while noncanonical signaling is linked with high-risk features. Branch-specific genetic manipulations and clinically relevant models should be employed in future research to maximize therapeutic strategies.

IRS2 amplification represents a recurrent but non-universal molecular alteration enriched in a subset of colorectal cancer brain metastases, with mechanistic links to β-catenin signaling and mitochondrial metabolism. Preclinical inhibition of IRS2/IRS1-2 demonstrates translational promise, positioning IRS2 as a context-dependent vulnerability and potential therapeutic target in selected CRC brain-metastatic tumors.

Critically, the STAT3 inhibitor S3I-201 abrogated the pro-tumorigenic effects of BMX overexpression on HT29 cell proliferation, migration, and invasion. In conclusion, our findings establish that BMX drives CRC progression by activating STAT3 signaling pathway, which subsequently suppresses E-cadherin expression to induce EMT.

In addition, the use of a JAK2 inhibitor (WP1066) and agonist (C-A1) verified that Mel exerted its protective effects by down-regulating the JAK2/STAT3 pathway. Morris water maze further confirmed that Mel improved spatial learning and memory function in neonatal rats with HIBD. Multimodal MRI offers a visual basis for monitoring metabolic changes and therapeutic effects, while Mel enhances neurogenesis and mitigates brain injury through inhibition of the JAK2/STAT3 pathway, thus providing a theoretical basis for the clinical application of Mel in HIBD in neonates.

P2, N=176, Recruiting, Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting --> Recruiting