P2, N=54, Completed, Hospices Civils de Lyon | Unknown status --> Completed | Trial completion date: Oct 2023 --> Jun 2026 | Trial primary completion date: Oct 2023 --> Jun 2026

Combining SDUY104 with an ERK inhibitor Ulixertinib produced synergistic antiproliferative activity via enhanced MAPK suppression. In a PANC-1 xenograft model, combination of SDUY104 with BKM-120 exhibited superior antitumor activity compared to either monotherapy. Collectively, this study identifies a potent SHP2 allosteric inhibitor and delineates a critical compensatory signaling mechanism underlying resistance to SHP2-targeted therapy, providing proof-of-concept support for pancreatic cancer treatment.

In addition, mTOR pathway activity and responsiveness to mTOR inhibitors (rapamycin and ipatasertib) and chemotherapeutic agents (cisplatin) were assessed. Compared with 2D monolayer cultures, 3D TMSs exhibited reduced mTOR signaling activity, which led to significantly decreased sensitivity to mTOR inhibition. These findings indicate that 3D bioprinted breast cancer models recapitulate key structural and signaling features of in situ tumors more accurately than 2D systems, highlighting their potential value for preclinical drug testing and mechanistic studies.

IL-22 promotes LUAD progression by activating the PI3K/AKT signaling pathway and inducing EMT, while its upregulation is modulated by promoter hypomethylation and miR- 21-5p suppression. The IL-22/PI3K/AKT axis represents a potential therapeutic target for LUAD management.

This nine-BRM prognostic model serves as a potential prognostic stratification tool that may complement existing clinical parameters in evaluating the outcomes of KIRC patients.

The obtained results revealed that BiNPs-NISM-Dox-Pi3Ki@BSA-GSH-Glu nanosystem could be considered as a novel promising combinational therapy approach to overcome conventional limitations of current glioma cancer treatments through targeted drug delivery, signaling pathway inhibition, chemoradiotherapy. Further investigations including in vivo and clinical studies for assess reducing the side effects of drugs and optimum efficacy is required.

Notably, the PI3K/mTOR inhibitor BEZ235 abolished the pro-malignant effects and reversed the autophagy suppression induced by WDR72 overexpression. Collectively, our findings establish that WDR72 acts as an oncogene in ESCC by promoting proliferation, survival, and metastasis via activating the PI3K/Akt/mTOR signaling to suppress autophagy.

This study identified oxidative stress-correlated DEGs and prognostic risk model in sevoflurane-treated GBM for computationally predicting potential immunotherapy response and drug sensitivity. Therefore, THBS1 mediated a protective response against sevoflurane-induced cytotoxicity and migration inhibition in GBM via PI3K/AKT activation, highlighting a potential molecular interaction between anesthetic exposure and tumor cell behavior.

In xenografts, PAC-XL outperformed cetuximab, BGT226 and alpelisib, including complete regressions, while reducing hyperglycemia and weight loss caused by systemic PI3K/mTOR inhibition. These findings establish targeted delivery of PI3K/mTOR inhibitors as a strategy to enhance efficacy while improving tolerability in HNSCC.

HMGA1 significantly promoted the proliferation, migration, and invasion of UM cells from different origins (primary C918, metastatic MUM-2B) by activating the PI3K/Akt pathway and upregulating MMP-9 expression, suggesting its potential as a target for molecular targeted therapy in UM.

Conversely, SLFN5 knockdown impaired the antitumor efficacy of the drug combination. In conclusion, the combination of Orlistat and Everolimus represents a promising therapeutic strategy for PanNETs, with SLFN5 serving as a critical mediator and potential biomarker for treatment efficacy.