P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Jan 2027

P1/2, N=92, Recruiting, InxMed (Shanghai) Co., Ltd.

RHBDD1 facilitates CC progression by promoting proliferation, EMT, migration, invasion, and tumorigenesis through activation of the EGFR/PI3K/AKT pathway, likely via direct receptor-level interaction. Targeting this regulatory node may offer a promising therapeutic approach for CC.

These findings position MEK1/2 and PI3K as promising therapeutic nodes for managing cutaneous HSV-1 infections. This host-directed dual-pathway inhibition may therefore help reduce recurrent orolabial HSV-1 lesions.

A combination of defactinib and the MDM2 inhibitors showed that nutlin-3a showed synergistic/additive effects in wild-type and antagonistic effects in mutated TP53 cells, whereas RITA retained synergistic activity in mutated TP53 cells. These results suggest that the therapeutic success of combined FAK and MDM2 inhibition in mesothelioma depends on the precise matching of MDM2 inhibitors with the TP53 genotypes, and highlight the need for genotype-based selection of MDM2 inhibitors.

These models were treated with FAK inhibitor IN10018 as monotherapy or in combination with anti-PD-1 immunotherapy...FAK inhibitors can enhance the sensitivity of HCC to anti-PD-1 therapy by inhibiting angiogenesis and fibrosis and promoting CD8+ T cell infiltration. This effect exceeds the efficacy of the current first-line treatment, highlighting FAK inhibition as a novel and promising therapeutic strategy for HCC.

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.