EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1)

Pharmacologic interventions using rapamycin and Jagged-1 further validated that Gln modulates the mTOR/Notch1 signaling cascade, leading to increased MUC2 expression and improved mucosal integrity. Collectively, these results demonstrate that Gln confers robust protection against RIII by regulating the mTOR/Notch1 axis, alleviating Notch1 overactivation, and promoting GC differentiation. These findings provide valuable mechanistic insight and experimental support for Gln as a potential therapeutic agent to prevent or mitigate radiation-induced intestinal injury.

The mechanistic target of rapamycin (mTOR) is a central regulator of cell growth and a promising cancer therapeutic target...In the HGC-27 xenograft mouse model, oral administration of T133 exhibited dose-dependent efficacy comparable to clinical-stage inhibitor PF-04691502, while exhibiting significantly reduced hepatotoxicity, nephrotoxicity, and pulmonary toxicity. Moreover, assessments of T133 on cytochrome P450, hERG, and AMES indicate a favorable safety profile. These findings suggest T133 is a promising mTOR inhibitor, warranting further investigation for cancer therapy.

Taken together, our results identify a distinct type of ribosome-enriched SGs that form through RNA-ribosome condensation rather than classical translational stress pathways. This mechanism provides a direct example of how a clinically used drug can reorganize cytoplasmic RNA-protein complexes, with possible consequences for mRNA regulation, cancer therapy, and neurodegenerative disease.

Mechanistically, these effects were accompanied by reduced phosphorylation of p70S6K (Thr389, Ser421/424) and increased p-4EBP1, indicating inhibition of mTORC1 signaling. These findings suggest that d1 and d3 are promising lead compounds with dual antiproliferative and anti-migratory activity in cervical cancer, mediated through modulation of the PI3K/Akt/mTOR axis.

Analysis of human SCC specimens revealed elevated 4E-BP1 phosphorylation together with increased proliferative and angiogenic markers and activation of the mTOR signaling pathway, mirroring molecular features observed in 4E-BP1-deficient tumors. Collectively, these findings establish 4E-BP1 as a tumor suppressor in skin carcinogenesis that constrains both proliferative and angiogenic processes, underscoring the contribution of dysregulated translation to SCC development.

Our study suggests that D-2-HG plays a significant role in the pathogenesis of GBM by modulating specific genes and signaling pathways. Utilizing machine learning techniques, we identified six essential regulatory genes, and further molecular docking simulations revealed a strong affinity of D-2-HG for these critical targets. Collectively, these results establish a substantial basis for future investigations into the mechanistic role of D-2-HG in GBM oncogenesis.

P2, N=17, Terminated, Dana-Farber Cancer Institute | N=47 --> 17 | Active, not recruiting --> Terminated; participants are no longer being examined or receiving intervention

These findings uncover a previously unrecognized role of valine as a direct molecular controller of the cancer cell cycle, acting through translational repression of D-type cyclins. Targeting exogenous valine supply, in combination with cell-cycle-directed therapies, may offer a promising strategy to suppress the growth of malignant tumors.

P2, N=47, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Nov 2025 --> May 2026

Repeated vobra duo doses ameliorated this outcome, reverting rhabdomyosarcorma to rhabdomyoma tumor, by increasing Desmin and Myogenin/Myf-4 differentiation markers expression, and reducing both Ki-67 and CD133. In conclusion, the in vitro and in vivo anti-tumor effects towards pSC highlight the need to extend the investigation to patient-derived preclinical models, to pave the way for clinical translation.

The current study is the first to demonstrate an association between preoperative inflammatory biomarkers, opioid consumption, and acute postoperative pain after VATS in patients with lung cancer. Future studies are needed to confirm these findings.

Together, our results demonstrate that b14 is an excellent novel small-molecule inhibitor of eIF4E for future cancer therapy.