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

PK/PD-guided screening on the NOCS prioritized Paxalisib, which, when combined with the exon skipping approach, demonstrated synergistic anticancer efficacy in patient-derived tumor models. These findings establish a clinically relevant framework that integrates multi-organ PK/PD modeling with genotype-driven therapeutic strategies, highlighting the potential of combining targeted gene correction with small-molecule therapy for personalized treatment. This platform offers broad applicability in precision oncology and drug development across diverse genetic contexts.

P2, N=29, Not yet recruiting, Sabine Mueller, MD, PhD

These pro-tumor effects were partially reversed by pharmacological inhibitor BEZ235 for PI3K/mTOR. In vivo validation using a mouse xenograft model confirmed that PFOS exposure promotes tumor growth and upregulates the same pathway and effector molecules. This study provides integrated clinical and experimental evidence that PFOS exposure at environmentally relevant concentrations promotes PTC progression by inducing PI3K/AKT/mTOR-mediated EMT and associated enzyme secretion, providing crucial experimental evidence for the toxic role of PFOS as an environmental contaminant in thyroid tumors and underscoring the urgent need for enhanced environmental health risk assessment and regulation.

Targeting the ATM/PLK1/GPI axis through combinational treatment with rigosertib may therefore represent a therapeutic strategy. Moreover, PLK1 expression and GPI pT215 levels may serve as potential candidate markers for GBM. Collectively, activation of the ATM/PLK1/GPI axis plays a critical role in regulating PPP flux and TMZ resistance in GSCs.

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.

P1, N=75, Suspended, Dana-Farber Cancer Institute | Trial completion date: Jan 2026 --> Jan 2027 | Recruiting --> Suspended | Trial primary completion date: Dec 2025 --> Dec 2026

P1, N=26, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed

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.

P1/2, N=18, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Jul 2026 --> Feb 2026 | Trial primary completion date: Jul 2026 --> Feb 2026

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.