dactolisib (RTB101)

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.

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.

OncoPredict suggested higher sensitivity in the high-risk group to 5-fluorouracil, PI3K-AKT-mTOR inhibitors (afuresertib, pictilisib, taselisib, dactolisib), and the MET inhibitor savolitinib. Multi-omic integration of PCD-related genes delineates PCD-driven heterogeneity in AML and yields a robust five-gene prognostic model with therapeutic implications. CORO1A emerges as a potential apoptosis-associated oncogene that promoting AML cell survival.

The prognostic model constructed based on ferroptosis-related lncRNAs demonstrates considerable reliability. It not only effectively predicts patient survival but also reflects tumor immune status and drug response characteristics, showing potential as an auxiliary tool for prognosis assessment and personalized treatment in DLBCL.

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.

Reversible resistance to NVP-BEZ235 in ccRCC is driven, at least in part, by an m6A-dependent YTHDF3-SYNM axis. Targeting YTHDF3 or SYNM may provide a rational strategy to overcome PI3K/mTOR inhibitor resistance in ccRCC.

In a MECOM-r AML PDX model, mivebresib with dactolisib or LCL161, was superior to monotherapy or vehicle in reducing AML burden and increasing mouse survival. These findings highlight that cotreatment with BETi and PI3K/mTOR or IAP inhibitor exerts superior in vitro and in vivo efficacy in MECOM-r AML cells and support further evaluation of these BETi-based combinations.

Co-inhibition of mTOR or the SLC3A2/SLC7A5 complex using dactolisib or JPH203 restores sensitivity to KRAS inhibitors in vitro and in vivo. These findings support combinatorial targeting of mTOR signaling or amino acid transport to overcome intrinsic resistance in KRAS-mutant lung cancer.

Mechanistically, FFAs were found to trigger Akt activation, and pharmacological inhibition of this protein by BEZ235 could successfully counteract their cancer-promoting effects. Collectively, these results support the presence of an EV-driven bidirectional interplay between PCa cells and adipocytes, which reprograms the latter toward a lipolytic, tumor-promoting phenotype.

Triple-Negative Breast Cancer can develop resistance to gemcitabine and overcoming this resistance is critical for effective treatment. In silico analysis using GEPIA revealed a relation between hENT1 with Mcl-1 and Bcl2. These findings reveal ABT-737 and NVP-BEZ235 attenuate MDA-MB-231GEMR cell line and show potential implication on reversing resistance in TNBC for further studies.

Through drug sensitivity analysis, several drugs exhibited significant correlation with risk score, and molecular docking illustrated that both dactolisib and linsitinib were capable of binding tightly with most signature genes, making them potential candidates for targeted therapeutic approaches of LGG. Thus, this model can stratify LGG patients with distinct gene expression features, immune landscape, genomic instability and microbiota features. By stratifying patients with risk score, this risk model may improve the accuracy of prognostic prediction for LGG patients, which might provide new insights into the molecular targeted therapy for individual treatment in a risk score-specific manner.

mTOR inhibitors such as everolimus and BEZ235 have demonstrated efficacy in pancreatic neuroendocrine tumors (PanNET) at the cost of severe side effects, and no biomarker currently predicts response. High expression of CAIX and LDHA, two markers of pseudohypoxia/glycolysis, was associated with shorter progression-free survival in patients treated with everolimus. This study demonstrates that tissue culture can effectively assess drug response in PanNET and identifies a pseudohypoxic/glycolytic profile as a determinant of resistance to mTOR inhibition, detectable by immunohistochemistry and potentially noninvasively by 18FDG PET-CT.