EIF4G1 (Eukaryotic translation initiation factor 4 gamma, 1)

Drug-gene mapping revealed candidates spanning those already in clinical trials for HNC (e.g., Afatinib, Cabozantinib, Dasatinib, Brigatinib, Lenvatinib, Capivasertib, and Erdafitinib) and emerging or repurposing candidates (Amuvatinib, XL765 (Voxtalisib), Golotimod, Artenimol, Quercetin, and Acetylsalicylic Acid), offering opportunities for precision repurposing...HPV stratification enhances precision, literature-based validation strengthens confidence, and integrated drug mapping enables refinement of existing therapies and discovery of novel candidates for personalized treatment strategies. Code Availability: The full implementation of the GARD pipeline, including preprocessing scripts, statistical analysis modules, and visualization tools, is publicly available on GitHub.

The journal retracts the article titled, "HSP70-eIF4G Interaction Promotes Protein Synthesis and Cell Proliferation in Hepatocellular Carcinoma" [...].

Melanoma A375 (vemurafenib [VEM]-sensitive) and A375R (VEM-resistant) cells were exposed to eIF4Fi RocA at varying doses and durations in vitro...Combined CR-1-31-B, EZH2i, and AKT1i effectively overcame resistance to RocA and VEM resistance both in vitro and in vivo. The eIF4F complex inhibitor reactivates ERK1/2-EZH2 and AKT1 signaling pathways, resulting in resistance to both eIF4Fi and VEM. Combined administration of an eIF4Fi with EZH2 and AKT1 inhibitors effectively enhances sensitivity to both eIF4F complex and BRAF inhibitors.

Disruption of this CELF1/eIF4E interaction inhibits both EMT induction in vitro and experimental metastasis in vivo. Our findings define a novel, non-canonical mode of translational regulation underlying cellular de-differentiation, raising the possibility that analogous non-canonical modes of translation impact additional transitional cellular states within development and disease.

Notably, combining the EBNA1-targeting PROTAC degrader EP-1215 with anti-PD-1 effectively restored IFN signaling, enhanced T-cell infiltration, and suppressed EBNA1+ tumors in humanized mice. This viral exploitation of RNA editing suggests that targeting EBNA1 could be a strategy to convert "cold" tumors into "hot" targets amenable to ICB therapy.

Drug-gene mapping revealed candidates spanning already in clinical trials for HNC (e.g. Afatinib, Cabozantinib, Dasatinib, Brigatinib, Lenvatinib, Capivasertib, Erdafitinib) and emerging or repurposing candidates (Amuvatinib, XL765 (Voxtalisib), Golotimod, Artenimol, Quercetin, and Acetylsalicylic Acid), offering opportunities for precision repurposing...These included targeted therapies such as Fostamatinib, Nintedanib, Brigatinib, Regorafenib, and Lenvatinib, as well as emerging compounds like Artenimol, Quercetin, and Acetylsalicylic Acid (Aspirin). Through a combination of genomic analysis, network expansion, and literature validation, the GARD pipeline offers a powerful way to accelerate personalized cancer treatments while reducing cost and development time.

Recent advances reveal that, beyond cis-regulatory uORFs, trans-acting factors such as translation initiation factors and associated RNA-binding proteins critically influence ATF4 translation. Understanding these mechanisms provides insight into ISR plasticity and its implications for development, aging, and disease.

Unexpectedly, eIFTerminator4 also caused a decrease in eIF4A and eIF4G levels, leading to a reduction in overall protein translation in cells. Our findings establish proof-of-concept that CBL can function as a degrader E3, expanding the arsenal of E3s available for targeted protein degradation in combating challenging drug targets.

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

Importantly, our results revealed that the PAK1 inhibitor, PF3758309, exhibited a profound synergistic effect with oxaliplatin in CRC. Collectively, our study unveils a novel function of PAK1 in CRC progression. Thus, these results highlight the potential of targeting PAK1 as a therapeutic strategy in CRC, particularly in combination with oxaliplatin.

Collectively, our findings reveal that KRT14 contributes to chemoresistance in BLCA not only via its structural roles but also by directly regulating translational machinery through eIF4H, leading to upregulation of the metabolic enzyme ACOX2. The newly defined KRT14-eIF4H-ACOX2 axis orchestrates lipid metabolic reprogramming and cell survival, underscoring the KRT14-eIF4H interface as a promising therapeutic target for overcoming cisplatin resistance in BLCA.

TOPK inhibitors reshape tumor immunometabolic microenvironment to trigger anti-tumor immunity in GC. The IFN-γ-TOPK-eIF4F-STAT1-PD-L1/IDO1 axis as a crucial regulator of the tumor immunometabolic microenvironment and provide novel insights into the combination of targeted therapy and immunotherapy for GC treatment.