P2, N=120, Not yet recruiting, BeBetter Med Inc

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.

The results indicate that, in addition to off-target interactions with members of the AGC kinase family predicted for most ATP-competitive inhibitors, Ipatasertib and NTQ1062 may exhibit strong interactions with PI3Kα, a member of the PI3K kinase family, while NTQ1062 may also interact with mTOR, a member of the PI3K-related kinase family. However, further in vitro and in vivo studies are required to validate these potential interactions. Overall, this work establishes a hybrid deep learning and physics-based computational framework for predicting the off-target effects of ATP-competitive AKT1 inhibitors and provides mechanistic insights into kinase cross-reactivity within the PI3K/AKT/mTOR signaling pathway.

We established a novel lactylation-related risk signature that effectively stratifies CRC patients by prognosis and TME characteristics. By elucidating the crosstalk between metabolic dysregulation, stromal barriers, and immune exclusion, this study provides potential biomarkers and stratified therapeutic strategies-ranging from standard chemotherapy to targeted metabolic and stromal interventions-to optimize precision medicine for CRC patients.

P2, N=29, Recruiting, Sabine Mueller, MD, PhD | Not yet recruiting --> Recruiting

P1, N=31, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Dec 2026 --> Jun 2026 | Trial primary completion date: Dec 2026 --> Jun 2026

P2, N=110, Recruiting, Dana-Farber Cancer Institute | N=180 --> 110

Further used of BGT226 (20 nm), a dual inhibitor of the AKT/mTOR pathway, inhibited the migration and invasive movement of CRC cells induced by HSP60 overexpression...This may be related to HSP60 overexpression activating AKT/mTOR signaling. These data suggest that HSP60 may be used as another important molecular target for the prevention and treatment of CRC.

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.

YY‑20394 (linperlisib), a highly specific PI3Kδ inhibitor, has demonstrated promising efficacy in a variety of hematological malignancies in clinical trials. In summary, YY‑20394 is effective for inhibiting proliferation of AML cells, and its combination with ABT199 has synergistic pro‑apoptotic effects in MV‑4‑11 cells, which provides new insights and potential avenues for the treatment of AML and its subtypes. Further studies are warranted to explore the therapeutic efficacy and underlying molecular mechanisms of this combination in additional AML subtypes.

Importantly, combining the PI3K/AKT inhibitor PKI-587 with the PARP inhibitor BMN673 synergistically inhibits tumor growth across multiple SCLC models, including cell lines, patient-derived organoids, and xenograft models. Collectively, our findings define a "PI3K/AKT-STAT5A-TRIM21-PARP1" axis critical for SCLC progression and propose its dual inhibition as a promising therapeutic strategy.

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.