AVTX-006

Drug sensitivity analysis revealed differences in the IC50 values of OSI-027, PLX-4720, UMI-77, and Sapitinib between the high-risk and low-risk groups. Enrichment analysis revealed that these prognostic ARGs were primarily enriched in pathways and biological processes related to tumorigenesis. The risk model of ARGs can effectively predict READ prognosis and provide potential therapeutic targets.

The study used mTOR kinase inhibitors: Everolimus and Torkinib; dual PI3K/mTOR inhibitors BEZ-235 and Omipalisib; and the mTORC1/2 inhibitor OSI-027. These compounds were used both as monotherapy and in combination with the MEK1/2 inhibitor AS-703026...The morphology of cells also changed significantly: their thickness, volume, roughness, convexity of shape, and irregularity, which may be a good diagnostic and prognostic factor for the response to treatment. Our studies to date on the effect of three generations of mTOR kinase inhibitors on the inhibition of the invasion process, the activation of apoptosis, and the reduction in cell proliferation suggest that they may be an important target for anticancer therapy.

Notably, both chloroquine treatment and ULK1-S757E transfection abolished the OSI-027/WZ4003 synergy. Moreover, elevated ARK5 expression was observed in HCC specimens and was independently associated with an unfavorable recurrence-free survival (RFS). Our findings propose a novel strategy for augmenting sensitivity to OSI-027 in HCC, further underscoring the significance of ARK5 and autophagy as cancer therapeutic targets.

Moreover, both excessive macropinocytosis induced by OSI-027 and macropinocytosis inhibition via CFL1 depletion suppressed β-catenin-driven tumor growth in orthotopic hepatocellular carcinoma model mice. Targeting macropinocytosis represents a promising therapeutic strategy for β-catenin mutant cancers.

Our prognostic signature effectively predicts LSCC prognosis, with MMP3 identified as a potential novel biomarker for LSCC treatment. Furthermore, our findings underscore the critical role of immune-based therapies in improving outcomes, especially for low-risk patients.

Furthermore, bioinformatics analyses showed that drugs such as erlotinib, OSI-027, and ibrutinib selectively targeted the CSC-specifically expressed genes. In conclusion, our results represent the first comprehensive characterization of CSCs properties in LSCC at the single-cell level.

Based on GDSC database, KLF3 upregulation was identified to be associated with higher sensitivities towards PI3K-Akt-mTOR pathway inhibitors such as PI-103, PIK-93, and OSI-027. In addition, patients with down-regulated KLF3 expressions were found more sensitive towards Trametinib, Cetuximab, and Erlotinib. Collectively, our findings suggest that KLF3 may act as a suitable biomarker for prognosis prediction, tumor microenvironment (TME) phenotype identification, thereby helping ccRCC patients to make better therapeutic decisions.

The following inhibitors were used: protein kinase inhibitors such as AKT-MK-2206, MEK-AS-703026, mTOR-everolimus and Torkinib, as well as dual PI3K and mTOR inhibitor-BEZ-235 and Omipalisib, and mTOR1/2-OSI-027 inhibitor in single-mode and their combinations with MEK1/2 kinase inhibitor AS-703026. There is a need for research on the search for new therapeutic strategies aimed at particular groups of patients. Effect of three generations of mTOR kinase inhibitors on caspase-3 activity, apoptosis and proliferation in melanoma cell lines.

Thus, the bromodomain inhibitor RVX-208 significantly augmented the therapeutic effects of the dual mTORC1/2 inhibitors, OSI-027 and PP242, both in vitro and in a human xenograft murine model. While single RVX-208 treatment induces apoptosis and a single mTORC1/2 inhibitor induces macropinocytosis, their combined treatment led to necroptosis-mediated cell death. These data suggest that combined treatment with drugs targeting BRD4 and mTORC1/2 may be an effective therapeutic intervention for drug-resistant RMS.

OSI-027 attenuates colon cancer progression through mediation of c-Myc/FOXO3a/PUMA axis. Thereby, this research might shed new insights on exploring the strategies against colon cancer.

Treatment of MERS-CoV- (IC: 0.618 µM) or SARS-CoV-2-infected (IC: 1.233 µM) Calu-3 cells with the mTOR inhibitor OSI-027 resulted in significantly reduced viral loads. Collectively, our study identified hnRNP C as a key regulator of MERS-CoV-perturbed circRNAs and their cognate mRNAs, and the potential of targeting hnRNP C-related signalling pathways as an anticoronaviral strategy.

Moreover, survival as well as anti-apoptotic signaling was impaired upon the use of OSI-027 as determined by AKT and MAPK blotting. Dual targeting of mTORC1/2 might therefore be a viable option for anti-neoplastic therapy in CCA.