2023年8月8日 · Here, we show that an eIF4A inhibitor, which targets a component of eIF4F, dramatically enhances the effects of KRAS G12C inhibitors in NSCLCs and together these agents induce potent tumor regression in vivo. By screening a broad panel of eIF4F targets, we show that this cooperativity is driven by effects on BCL-2 family proteins.

2023年6月29日 · Here, we show that an eIF4A inhibitor, which targets a component of eIF4F, dramatically enhances the effects of KRAS G12C inhibitors in NSCLCs and together these agents induce potent tumor regression in vivo. By screening a broad panel of eIF4F targets, we show that this cooperativity is driven by effects on BCL-2 family proteins.

2019年6月6日 · Translation initiation inhibitor rocaglates have been identified as the most potent drugs in MYC-driven lymphomas as they efficiently inhibit MYC expression and tumor cell viability. We found...

To explore the therapeutic mechanism of eIF4A inhibition against MYC-amplified G3-MB, we firstly measured the time-dependent changes of MYC protein levels of MYC-amplified G3-MB cells in response to CHX (20 μg/mL) or silvestrol (0.01 μM) within 24 hours. OTX2 and EIF4A1 were also tested in parallel as controls.

2024年11月8日 · Eukaryotic initiation factor 4 A (eIF4A) plays critical roles during translation initiation of cellular mRNAs by forming the cap-binding eIF4F complex, recruiting...

2023年6月29日 · We demonstrated that inhibition of translation in CLL targets the MYC oncogene, leading to decreased proliferative capacities and reversion of metabolic rewiring. Finally, we identified PHBs as direct interactors of the eIF4F machinery and as crucial factors for translation in CLL cells.

2023年12月12日 · The eIF4A is a relevant vulnerability in KRAS mutant NSCLC. In KRAS-driven tumors with high MYC levels, treatment with KRASi or MEKi induces a cytostatic response. This response is dependent on the balanced ratio between the apoptosis regulator BAX protein and the BCL-xL, as well as between the Bcl-2 homology 3-only protein Bim and the induced ...

2021年5月17日 · We propose that targeting eIF4A, as well as mutant KRAS, provides novel methods to improve the efficacy of anti-PD-1 and associated ICB therapies against PDACs, in which ARF6 and AMAP1 overexpression, as well as KRAS mutations of cancer cells are biomarkers to identify patients with drug-susceptible disease.

We demonstrated that eIF4Ai (silvestrol and rocaglamide A) reduced anti-IgM-induced global mRNA translation in CLL cells and also inhibited accumulation of MYC and MCL1, key drivers of proliferation and survival, respectively, without effects on upstream signaling responses (ERK1/2 and AKT phosphorylation).

2021年12月14日 · Overexpression of eIF4A1 downregulated E-cadherin expression through the c-MYC/miR-9 axis, which promoted EMT and metastasis of pancreatic cancer cells. Despite the potential feedback loop between eIF4A1 and c-MYC, RocA monotherapy is a promising treatment inhibiting eIF4A1-induced PDAC metastasis.