Our findings reveal a reciprocal regulatory relationship between FAK and ROR1, with both proteins enriched in CLL cells that have exited the lymph nodes. Given defactinib's favorable safety profile in solid tumor trials, combining FAK inhibition with BTK inhibitors could enhance therapeutic efficacy by limiting leukemic clone adaptability and addressing resistance and relapse. While anti-ROR1 therapies showed limited efficacy as monotherapy in CLL trials, targeting multiple nodes of this regulatory network may prove more effective.

The immunosuppressive effect mediated by MAPK12 overexpression was blocked by the PI3K inhibitor LY294002. MAPK12 knockdown restricted tumor growth and extended survival in mice, accompanied by increased CD8+ T cell infiltration. In summary, MAPK12 promotes HCC immune escape by upregulating PD-L1 via the PI3K/Akt/mTOR pathway.

P1, N=31, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

P1/2, N=4, Not yet recruiting, Verastem Inc.

By applying the pathway inhibitor LY294002, it was confirmed that the PI3K/Akt pathway is crucial for osteosarcoma proliferation. This study confirms that PYCR1 drives osteosarcoma cell proliferation and migration through three key mechanisms: regulating downstream genes, inhibiting ferroptosis, and activating the PI3K/Akt signaling pathway.

P1, N=24, Not yet recruiting, Capital Medical University

GOLPH3, which is overexpressed in PRAD, may enhance glucose metabolic activity in PRAD cells in association with activation of the PI3K/AKT/mTOR pathway, thereby supporting PRAD cell proliferation. These findings provide basic mechanistic evidence for the role of GOLPH3 in PRAD cell metabolism, but further clinical studies are required to determine its prognostic or therapeutic relevance.

Furthermore, the PI3K/AKT inhibitor LY294002 enhanced the effects of sh-MUC1 on the proliferation, apoptosis, migration, invasion and EMT progress, while the activator SC79 partially restored these effects...To conclude, these findings suggested that MUC1 played an important role in lung cancer progression, potentially through the PI3K/AKT pathway. This positioned MUC1 as a molecule worthy of further investigation for its therapeutic potential.

At single-cell resolution, this study characterizes the LMIC population in PDAC and implicates a CAF-associated SEMA3A-NRP1 signaling axis within their spatial and functional microenvironmental niches. These findings provide a refined conceptual framework for the development of prospective targeted strategies aimed at disrupting early microenvironmental cross-talk associated with PDAC liver metastasis.

EIF3B activated PI3K/AKT signaling and EMT, both of which were abolished by miR-124-3p or LY294002. These findings define the miR-124-3p/EIF3B/PI3K-AKT axis as a key regulator of OSCC progression and suggest EIF3B as a potential prognostic biomarker and therapeutic target.

P1, N=3, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=23 --> 3

PI3K/AKT/mTOR pathway activity was examined by Western blot, and its function validated using SC79 (AKT activator) and LY294002 (PI3K inhibitor)...By modulating the PI3K/AKT/mTOR signaling axis and the pro-angiogenic microenvironment, ADGRD1 facilitates tumor growth and neovascularization. ADGRD1 may serve as a promising prognostic biomarker and therapeutic target for advanced BLCA.