P1/2, N=24, Terminated, Institut Paoli-Calmettes | N=106 --> 24 | Suspended --> Terminated; Drug development withdrawn

Notably, LY294002 (a PI3K inhibitor) and Anisomycin (a JNK activator) partially reversed the anti-apoptotic and anti-inflammatory effects of PTE, respectively. This study provides the first integrated evidence combining network pharmacology and experimental validation that PTE protects against LIRI by modulating the PI3K/AKT and JNK/c-Jun signaling pathways, offering novel pharmacological insights into its translational potential in LIRI.

P1, N=46, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Jul 2027 | Trial primary completion date: Jun 2026 --> Jul 2027

FGFR2 is lowly expressed in DFU and can exert a protective effect by activating the PI3K/Akt pathway. It is a candidate diagnostic biomarker and potential therapeutic target for DFU.

P2, N=57, Active, not recruiting, Royal Marsden NHS Foundation Trust | Recruiting --> Active, not recruiting | N=324 --> 57 | Trial completion date: Sep 2026 --> Jun 2027 | Trial primary completion date: Sep 2026 --> Jun 2027

P1/2, N=54, Recruiting, Celcuity Inc | Trial completion date: Nov 2027 --> Jan 2030 | Trial primary completion date: Nov 2025 --> Jan 2028

Mechanistically, APOE overexpression significantly activated the PI3K/AKT signaling pathway, and this effect was effectively reversed by the PI3K inhibitor LY294002. Consistently, APOE overexpression enhanced tumor growth in vivo. These findings indicate that APOE promotes glioma progression through nuclear activity and activation of the PI3K/AKT signaling pathway, highlighting APOE-related signaling as a potential therapeutic target in glioma.

Hepatocellular carcinoma (HCC), lung adenocarcinoma (LUAD), and ovarian cancer (OC) cells with cisplatin-induced DNA damage were treated with lactate at a concentration gradient, Endothelial cell-specific molecule 1 (ESM1) shRNA, ESM1 overexpression plasmid, or the Protein Kinase B (AKT) Serine/Threonine Kinase 1 (Akt1) inhibitor LY294002. Analysis of tumor patient samples further validates the negative correlation between ESM1 and CD8+ T cell levels in cancer patients. In summary, lactate activates the Akt1-Murine Double Minute 2 (MDM2)-p53 pathway via ESM1 to suppress DDR, while the reduction of DDR-generated dsDNA inactivates the cyclic GMP-AMP synthase-Stimulator of Interferon Genes (cGAS-STING) pathway, thereby inhibiting CD8+ T cell immune infiltration.

However, PRDX4 overexpression showed opposite effects, which were partly reversed by the ferroptosis inhibitor, ferrostatin-1 and the inducer erastin. Most crucially, PRDX4 depletion-mediated inactivation of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway could be rescued by 740 Y-P (a PI3K activator), whereas PRDX4 overexpression triggered the activation of the PI3K/AKT signaling pathway, which could be reversed by the PI3K inhibitor LY294002. Collectively, the data suggest that PRXD4 suppresses ferroptosis in ESCC cells by activating the PI3K/AKT signaling pathway, suggesting that targeting PRDX4 may be a novel strategy for treating patients with ESCC.

P1, N=210, Active, not recruiting, iOnctura | Trial completion date: Mar 2025 --> Mar 2027

Moreover, fimepinostat downregulated cytokine and chemokine secretion increased by merlin loss in schwannoma cells. Fimepinostat is a promising new drug intervention for NF2-SWN patients with the potential to promote tumor regression.

This study evaluated three potential anticancer agents targeting these pathways: buparlisib (a pan-PI3K/mTORC1 inhibitor), SN32976 (a PI3K p110α inhibitor), and pterostilbene (a resveratrol analogue that downregulates PI3K/AKT and NFκB signaling)...Growth in 3D collagen gels conferred drug resistance on OVCAR8 but not SKOV3 models. Overall, these findings provide preclinical support for further investigation of SN32976 and pterostilbene in ovarian cancer models.