MK-2206

The results suggest that latent improved outcome of high-risk BCR patients (mean PSA doubling time 4.4 months) on combined MK-2206+Bic versus Bic alone was attributable to a subgroup identified by crosstalk AR activation secondary to inhibition of AKT. Toxicity may affect tolerance of sustained AKT-AR inhibition.

In addition, AKR1C3 overexpression promoted aerobic glycolysis in HSCs by activating the AKT/mTOR pathway, but these effects were partly reversed by glycolysis inhibitors (2-DG) and AKT inhibitors (MK-2206). Our findings revealed the mechanism by which AKR1C3 promotes LF, suggesting that AKR1C3 may serve as a potential therapeutic target for LF, warranting further studies.

Additionally, wt-EGFR and pAKTSer473 protein complex formation in A549 cells was disrupted with an AKT inhibitor (MK2206), resulting in enhanced cytotoxicity in vitro. Our study demonstrates that EGFR-TKI response in wt-EGFR cells is dictated by BRG1 status. These findings propose screening of wt-EGFR NSCLC patients for BRG1 status for identifying individuals likely to benefit from EGFR-TKI therapy versus patients who will benefit from AKT inhibitor treatment.

Considering the metabolism of icariin into icaritin in vivo, icaritin was selected for in vitro study. Furthermore, MK2206 upregulated the expression levels of cleaved caspase-3 and p-p53(Ser15), as well as the Bax/Bcl-2 ratio, and downregulated the expression levels of p-Akt(Ser473) and p-MDM2(Ser166). These findings suggest that icariin protects against high-fat diet-induced spermatogonium apoptosis potentially through regulation of Akt/MDM2/p53 signaling and promotion of mitochondrial fusion.

MK-2206 and rapamycin suppressed the expression of ASS1 in H446-BR cell. In xenograft model, BCT-100 has little anti-tumor effect on H446-BR compared with H446 as well as H446-BR silenced sestrin3. Collectively, these results elucidate SESN3 plays an essential role in resistant mechanism, which will provide a valuable source of information for translational research.

Cells were treated with the Gli1 inhibitor Gant-61, the Smoothened inhibitors GDC-0449 and Glasdegib, the Akt inhibitor MK-2206, and the mTOR inhibitor RAD001, both alone and in combination. These findings demonstrate a functional interaction between Hh/Gli1 and PI3K/Akt pathways in T-ALL and identify Gli1 as a critical, druggable node. Dual targeting of Gli1 and Akt represents a potential therapeutic strategy to overcome resistance and improve treatment outcomes in T-ALL.

Interventions utilizing a range of inhibitors at the in vitro level, including the PDGFR-β inhibitor AG1296, the PI3K inhibitor LY294002, the AKT inhibitor MK2206, and the FAK inhibitor Y15, demonstrated that E. multilocularis protoscoleces protein (EmP) induces angiogenesis through PDGFR/PI3K/AKT/FAK signaling pathway. Our findings provide new perspectives on how E. multilocularis infection triggers pathological angiogenesis in the host liver, and may provide a novel anti-angiogenic therapeutic strategy against E. multilocularis infection.

These subtypes exhibited distinct drug sensitivities (C1 sensitive to panobinostat, MK-2206, 17-AAG; C2 sensitive to venetoclax) and predicted immunotherapy responses (C1 potentially benefiting more from anti-PD-1)...Crucially, aberrant PKM2 overexpression was linked to imatinib (IM) resistance...To mitigate vMO toxicity, IL3-Lamp2b-engineered exosomes were developed, demonstrating efficient vMO loading, targeted delivery to leukemia cells, potent PKM splicing correction, significant IM resistance reversal, and minimal stromal cell toxicity. This work defines glycolysis-based AML subtypes with therapeutic implications and establishes engineered exosome-delivered vMO as a promising strategy to overcome drug resistance in hyper-glycolytic myeloid leukemia.

Combinatorial effects with hormone therapies (tamoxifen, fulvestrant, and letrozole) and the AKT inhibitor MK2206 were evaluated. Xanthene- and pyran-based hybrids-particularly SJ028, SJ064, and SJ078-showed strong antitumor activity through apoptosis induction, cell cycle arrest, and PI3K/AKT pathway modulation. Their preserved efficacy in resistant models and synergistic interactions with hormone therapies contrasted with the antagonism observed with AKT inhibition, highlighting their potential as promising candidates for the treatment of hormone-responsive and -resistant cancers.

Exosomal miR-20b-5p represses MASTL, remodels PI3K-AKT, and attenuates Ara-C responses in AML models. Seed-mutant reporters and 3'-UTR-independent rescue support target specificity. Findings are mechanistic and hypothesis-generating; clinical relevance requires confirmation in primary blasts and prospective validation.

This work demonstrates that the adipogenically differentiated MSCs enhance the survival and chemoresistance of AML cells by modulating metabolic and signaling pathways. It provides integrated insights into the microenvironment-driven mechanisms of AML drug resistance and presents potential therapeutic targets to enhance treatment efficacy.

The in vitro results were confirmed with in vivo mouse models. 4EGI-1 strongly inhibited NPC growth and metastasis, and 4EGI-1 may develop as the potential therapy for the treatment of metastatic NPC.