P2, N=33, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2028 --> Feb 2029 | Trial primary completion date: Feb 2026 --> Feb 2029

Conversely, LY294002 inhibited the glycolytic enhancement and aggressive phenotypes induced by UCHL5 overexpression (P < 0.01)...UCHL5 activates the PI3K/AKT/mTOR cascade, which enhances the glycolysis of RCC cells and promotes the development of renal cancer. This study provides insights into the molecular mechanisms underlying the oncogenic role of UCHL5 in RCC.

Esketamine, a GRIN2D inhibitor, and LY294002, a PI3K inhibitor, either alone or in combination, could suppress the tumor growth induced by high GRIN2D levels both in vitro and in vivo. This study is the first to identify the involvement of GRIN2D in lung cancer and to clarify the underlying mechanism of its effect; the findings further suggest that ketamine in cancer treatment may extend beyond relieving pain and depression.

The present study investigated the mechanism by which Que regulates ATP‑binding cassette (ABC) transporter expression in MCF‑7 cells using a PTEN overexpression plasmid and the PI3K inhibitor LY294002...The results of the present study demonstrated that Que suppresses cell viability and induces apoptosis in MCF‑7 cells. Moreover, it enhances intracellular drug accumulation and downregulates ABC transporter expression by modulating the PTEN/PI3K/AKT signaling pathway.

Pharmacological inhibition of PI3K via LY294002 reversed MICALL2-induced angiogenesis. Therefore, MICALL2 facilitates CRC angiogenesis through the EGFR/PI3K/AKT/KLF5/VEGFA axis and may serve as a promising target for anti-angiogenic therapy.

Pharmacological inhibition of FAK with single agent VS-4718 did not significantly reduce macroscopic tumor volume; however, its use in combination with the mitogen-activated protein kinase kinase (MEK) inhibitor selumetinib resulted in both a significant reduction in tumor volume and the preservation of dorsal root ganglion architecture. Our findings establish a critical role for FAK in schwannoma development and provide rationale for evaluation of combination FAK plus MEK inhibition in future clinical trials for NF2-associated SWN.

Overexpression of IL7R was shown to alleviate CIRI by suppressing apoptosis. These findings indicate IL7R as a novel target for IS treatment.

P2, N=40, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2026 --> Mar 2027 | Trial primary completion date: Mar 2026 --> Mar 2027

EA at Foot Shaoyang meridian acupoints can alleviate inflammatory responses and bone loss in postmenopausal osteoporosis rats, and its mechanism may be related to the activation of the PI3K/AKT pathway.

Functional validation used a single OPCML small interfering RNA (siRNA) with a non-targeting siRNA control (siNC) in U87 and U251 cells with Transwell invasion, wound healing, colony formation, CCK-8 proliferation, and Western blotting for p-AKT and p-mTOR, with LY294002 rescue...Loss of OPCML aligns with proliferative programs and a GBM-specific immune pattern. These data nominate OPCML as a prognostic marker and a surface-level modulator that could be leveraged alongside RTK/PI3K axis inhibitors in GBM.

The oral drug combination was well tolerated with no dose-limiting toxicity or need for dose reduction over the 4 year period. The Avutometinib and Defactinib combination may represent a new standard treatment option for platinum-resistant and AI-resistant/recurrent LGSOC who have failed other MEKi.

Several FAK targeted inhibitors have advanced into clinical evaluation; for example, CEP-37440 is undergoing phase I trials, whereas GSK-2256098 has reached phase II trials. This review summarizes the structure and functional characteristics of FAK, its role in the pathogenesis of NSCLC, the research progress on FAK inhibitors, and the current status and prospects of combining FAK inhibitors with other therapies for NSCLC. The aim is to provide new insights for future clinical trial design and combination therapy strategies for NSCLC.