Critically, the use of a PI3K inhibitor (LY294002) demonstrated that the nicotine-induced downregulation of p53 and upregulation of MMP-2, as well as the enhancement of cellular invasion are dependent on PI3K/AKT pathway activation. These findings conclusively demonstrate that nicotine promotes the malignant transformation of HPV-16 positive cervical cancer cells by altering the expressions of MMP-2, p53, Caspase-3, and p21 via the activation of the PI3K/AKT pathway. This highlights the therapeutic potential of targeting this pathway in cervical cancer treatment.

Interventions utilizing a range of inhibitors at the in vitro level, including the PDGFR-β inhibitor AG1296, the PI3K inhibitor LY294002, the AKT inhibitor MK2206, and the FAK inhibitor Y15, demonstrated that E. multilocularis protoscoleces protein (EmP) induces angiogenesis through PDGFR/PI3K/AKT/FAK signaling pathway. Our findings provide new perspectives on how E. multilocularis infection triggers pathological angiogenesis in the host liver, and may provide a novel anti-angiogenic therapeutic strategy against E. multilocularis infection.

P1, N=12, Terminated, Henan Cancer Hospital | Phase classification: P1/2 --> P1 | Trial completion date: Feb 2025 --> Aug 2025

P2, N=40, Recruiting, Rhizen Pharmaceuticals SA | Trial completion date: Mar 2026 --> Mar 2027 | Trial primary completion date: Oct 2025 --> Dec 2026

When these cancer cells were treated with doxorubicin (ADM) and 5-fluorouracil (5-FU), cell survival rate was determined by MTT, apoptosis by TUNEL, and colony formation by colony formation assay. The cancer cells were treated with the PI3K/Akt pathway inhibitor LY294002, and the expression of drug resistance-related proteins MDR1, MRP1, BCRP, Livin, cIAP1, XIAP, Akt, p-Akt, p65, and p-p65 was detected by Western blotting...AFP regulates the expression of drug resistance-related genes by activating the PI3K/Akt/NF-κB signaling pathway. AFP plays a pivotal role in MDR of cancer cells, the mechanism may be involved in activating the PI3K/Akt/NF-κB signaling pathway.

Our study reveals for the first time that TAX restores osteogenic-adipogenic equilibrium in OP-BMSCs and promotes bone regeneration through PI3K/AKT/PPARγ activation and mitochondrial protection-mediated suppression of necroptosis. These results position TAX as a promising therapeutic candidate for osteoporosis.

Helicobacter rodentium exacerbates anti-NMDAR encephalitis by inducing PI3K/AKT-mediated Tfh/Tfr imbalance, highlighting a potential therapeutic target in autoimmune encephalitis.

Treatment with the PI3K inhibitor LY294002 effectively inhibited p-PI3K activation and substantially reduced HER2 expression. Immunohistochemistry (IHC) analysis confirmed a strong positive correlation between changes in HER2 expression and tumor radioactive uptake trends. This study highlights the pivotal role of HER2 as a dynamic biomarker in trastuzumab resistance and supports the integration of molecular imaging into clinical decision-making for personalized therapeutic adjustments in HER2-positive breast cancer.

The combined use of palbociclib and PIK75 synergistically inhibited the expression of the cell cycle proteins CCNE1, CDC6, and CDC25A, as well as the abnormal activation of PIK3CA and AKT phosphorylation. The combination of these two drugs synergistically inhibited tumor cell cycle progression and promoted apoptosis in vitro and in vivo, which provides a promising idea for the treatment of ESCC in the future.

Fimepinostat was tolerable at a dose of 35 mg/m2 in children with relapsed and refractory solid and CNS tumors, but lacked significant clinical activity. Discovery of drugs to target Myc continues to be a high priority for childhood cancers.

Comparative analysis with the MTOR-GDC-0980 complex confirmed consistent interaction patterns, reinforcing the structural stability and specificity of tiliacorinine. These results highlight its strong pharmacological potential and support its candidacy as a promising lead compound for cholangiocarcinoma therapy.

OPN enhances tumor proliferation and survival through mechanistic target of rapamycin and B-cell lymphoma 2 upregulation (e.g., via denticleless E3 ubiquitin protein ligase homolog in hepatocellular carcinoma) and drives metastasis via PI3K/AKT-mediated epithelial-mesenchymal transition and androgen receptor (AR) activation (e.g., via the OPN-RAN-AR axis in pancreatic cancer)...Therapies targeting the OPN-PI3K/AKT axis (e.g., PI3K inhibitors like LY294002) or combination treatments (e.g., with EGFR-TKIs) show promise for reversing drug resistance. Future research should focus on OPN isoform specificity, clinical translation, and interactions with autophagy and long non-coding RNAs to refine precision therapies. This review summarizes recent advances in understanding the molecular mechanisms, therapeutic targets, and clinical challenges of the OPN-PI3K/AKT axis in gastrointestinal tumors, providing a foundation for overcoming resistance and developing precision therapies.