P2, N=146, Active, not recruiting, Queen Mary University of London | Trial completion date: Jan 2026 --> Aug 2026 | Trial primary completion date: Jan 2021 --> Aug 2026

Mechanistically, we not only regulated the PI3K/AKT pathway using inhibitor LY294002 and activator 740Y-P but also specifically knocked down PI3K via small interfering RNA (siRNA) to confirm if SPINK4's function depends on this pathway...In vivo, SPINK4 overexpression activated PI3K/AKT, promoting tumor growth and M2 macrophage infiltration. Collectively, SPINK4 acts as an oncogene to promote macrophage recruitment and M2 polarization via PI3K/AKT, driving CRC malignant progression.

The PI3K inhibitor LY294002 reversed these pro-tumor and immunosuppressive effects. High COQ10B expression is closely associated with ESCC progression and poor prognosis. These malignant biological behaviors and the associated immunosuppressive tumor microenvironment are potentially mediated via the activation of the PI3K/AKT/HIF-1A signaling pathway.

The study identified CHEK1 as a key diagnostic gene for BC through 127 ML algorithms and SMR causal inference. By combining AI-assisted virtual screening and molecular docking, computational candidate compounds targeting CHEK1 were prioritized. These findings represent hypothesis-generating in silico predictions and require experimental validation before any therapeutic conclusions can be drawn.

The PI3K inhibitor LY294002 significantly reduces AP2A1 levels and inhibits MDK-induced malignant behaviors. Targeting MDK-related signaling pathways may offer new strategies for CRC treatment.

Functionally, BPA exposure promoted prostate cancer cell invasion and EMT, which were associated with activation of the PI3K/AKT and MMP signaling pathways, whereas the PI3K inhibitor LY294002 effectively attenuated BPA-induced invasive phenotypes in vitro and reduced tumor progression in vivo. Collectively, these findings provide mechanistic insights into BPA-driven prostate cancer progression and highlight the value of network toxicology-based approaches in environmental toxicology research.

Among these are histone deacetylase inhibitors (HDACis), receptor tyrosine kinase inhibitors, and novel agents such as ONC201 and unesbulin that target metabolic and epigenetic pathways respectively...Despite these advances, challenges such as drug delivery across the blood-brain barrier and therapeutic resistance persist, necessitating the development of combination therapies and innovative delivery methods. Ongoing research is focused on refining these strategies and exploring additional molecular and immunological targets to improve outcomes for children with DMG.

Mechanistic investigations utilized PFKFB3 overexpression, PI3K activator (740 Y-P), and inhibitor (LY294002) intervention experiments...In vivo experiments confirmed that Res treatment markedly diminished tumor size and mass, lowered Ki-67 proliferation marker, enhanced programmed cell death, suppressed PI3K/AKT signaling, decreased glycolytic enzyme levels, and elevated copper-dependent cell death mediators. Res exerts anti-AML effects by inhibiting the PI3K/AKT pathway while coordinately regulating aerobic glycolysis and cuproptosis in AML cells.

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

P2, N=108, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

This is the first report in clinical samples showing that ipatasertib efficiently depletes FOXP3+ regulatory T cells and results in increased infiltration of effector CD8+ T cells in the tumor microenvironment. This was associated with preliminary efficacy in a subset of patients with treatment-refractory glioblastoma (GBM).

The PI3K/AKT agonist 740Y-P and inhibitor LY294002 were employed to determine the contribution of this pathway to EMT regulation in breast cancer cells...In contrast, the agonist 740Y-P restored the decreased migration, invasion, and EMT phenotypes induced by UBD knockdown. Collectively, our data demonstrated that UBD plays a critical role in the malignant progression of breast cancer, highlighting its potential as a novel therapeutic target for breast cancer patients.