Additionally, PCDH1 activated the NF-κB pathway by promoting nuclear translocation of P65, and inhibition of NF-κB with SC75741 reversed PCDH1-induced EMT, confirming that PCDH1 promotes pancreatic cancer metastasis via the NF-κB/EMT axis. PCDH1 acts as an oncogene in pancreatic cancer, promoting cell invasion, migration, and EMT progression through the NF-κB signaling pathway, making it a potential therapeutic target.

P2, N=12, Suspended, National Neuroscience Institute | Not yet recruiting --> Suspended

We summarize the clinical translation progress of ACT001, including its safety and pharmacokinetic profiles, discuss emerging delivery systems such as micelles, and review the patent landscape of PTN derivatives. By integrating mechanistic insights with progress in clinical applications and drug delivery, this review provides a foundation for further mechanistic studies and supports the translational development of PTN-based therapies for respiratory disorders.

Furthermore, CDDO-Me did not compromise the antitumor efficacy of DOX/LAP in breast cancer cells. CDDO-Me protects against DOX/LAP-induced cardiotoxicity by stabilizing GPX4 and inhibiting ferroptosis, offering a promising therapeutic strategy that preserves cardiac function without interfering with chemotherapy.

Notably, 8 exhibited significant antitumor efficacy comparable to CDDO-Me (bardoxolone methyl), which had entered clinical trials. Taken together, 8 represents a promising candidate for the treatment of cancer and merits further study.

Molecular docking analyses supported the binding of CUR and DOX to key ferroptosis regulators. This study shows the potential of CUR to sensitize DOX-resistant cancer cells through ferroptosis-linked-oxidative stress targeting.

Molecular docking confirmed that LT4 stably occupied the ATP‑binding pocket of PI3Kγ with a binding energy comparable to wortmannin and a conformation similar to antroquinonol. In conclusion, to the best of our knowledge, the present study is the first to comprehensively demonstrate the multi‑target anti‑CRC effects of LT4, highlighting its potential as a therapeutic agent, especially in KRAS‑mutant CRC.

SLC12A8 promotes immune evasion and metastasis in Luminal B breast cancer by inducing CD8+ T-cell exhaustion via activation of the TLR signaling pathway, suggesting its potential as a prognostic biomarker and therapeutic target.

P1, N=20, Not yet recruiting, University Health Network, Toronto

Integrated mechanistic studies, including network pharmacology, transcriptomics, and Western blot analysis, indicated that the anti-leukemic effects of oleandrin are associated with suppression of the PI3K/AKT signaling pathway, as evidenced by reduced levels of key proteins such as PIK3CA, phosphorylated AKT (p-AKT), phosphorylated GSK3β (p-GSK3β), c-Myc, Bcl-2, and Bcl-xL. These findings suggest oleandrin is a promising therapeutic candidate for T-ALL, likely through suppression of the PI3K/AKT pathway.

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.

Emerging strategies to modulate NLRP3 include small-molecule inhibitors (e.g., MCC950, BAY-117082), plant-derived compounds (e.g., oridonin, Bacopa monnieri), and immunotherapy approaches, including intratumoral NLRP3 agonists combined with checkpoint blockade. This review synthesizes the multifaceted roles of NLRP3 in OSCC, highlighting its centrality in inflammation-driven tumor biology and its promise as a therapeutic target. Understanding the contextual duality of NLRP3 activation is critical for developing precision therapies that disrupt its tumor-supportive effects while preserving or enhancing its immunogenic functions.