EEF2K (Eukaryotic Elongation Factor 2 Kinase)

To further enhance tumor-specific delivery, we engineered A6@ZIF-8, a pH-sensitive nanocarrier that promotes drug accumulation at tumor sites compared to free A6, leading to improved therapeutic outcomes. Collectively, our data indicate that targeted degradation of eEF2K via PROTAC technology constitutes a novel and therapeutically relevant intervention strategy for TNBC.

Finally, the allograft mouse models ulteriorly validated that BVC impaired tumor growth and inhibited eEF2K signaling in vivo. Collectively, the present study demonstrated that BVC inhibited melanoma metastasis by targeting eEF2K/eEF2 signaling, and the inhibition of autophagy caused by BVC could further contribute to the anti-melanoma potency of BVC.

Recognizing the risk for first-degree relatives may potentially increase awareness of early symptoms among family members of HL patients, leading to earlier diagnosis and better outcomes. Conversely, understanding that the hereditary risk, though higher than in the general population, remains relatively low may provide reassurance for affected families.

These findings highlight the molecular heterogeneity of EOCRC and demonstrate the utility of multi-omic approaches in refining germline variant interpretation. Integrating tumour transcriptomics enhances gene discovery efforts and supports a more comprehensive understanding of CRC heritability in younger individuals.

Additionally, controlling sirtuin (SIRT), 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK), mechanistic target of rapamycin complex-1 (mTORC1), and autophagy/mitophagy flux via eEF2K modulation could help safeguard cardiomyocytes and endothelial cells from ischemic damage...Overall, targeting eEF2K offers a promising and complex strategy for CVD treatment. Further research into selective modulators, biomarker development, and clinical trials is essential to translate preclinical results into effective therapies.

Cyclin D1 was inhibited pharmacologically with palbociclib...Our findings reveal that eEF2K drives immune evasion in melanoma by stabilizing PD-L1 through Cyclin D1 suppression. Targeting the eEF2K-Cyclin D1-PD-L1 axis represents a promising strategy to augment immune checkpoint blockades and improve antitumor immune responses.

We also discuss emerging therapeutic technologies, such as proteolysis-targeting chimaeras (PROTACs) and non-coding RNAs (ncRNAs), which hold promise for future cancer treatments. We aim to offer clearer insights and guidance for developing novel strategies to inhibit eEF2K in cancer therapy, thereby broadening the range of treatment options for patients.

Furthermore, the probe maintained significant inhibition of cell proliferation, migration, and invasion, and enhanced the antitumor activity of paclitaxel in combination treatment. Therefore, a reliable and efficient toolkit would be provided for eEF2K mechanism study and corresponding drug discovery. Our work could also be beneficial to the study and establishment of TPD and the visualization of a dual-functional system.

In a recent study, Biltekin and colleagues [...].

Despite advancements in standard-of-care therapies, including surgery, radiotherapy, and temozolomide (TMZ), the median survival remains approximately 15 months, with a 5-year survival rate of less than 10%...Additionally, inhibiting the FOXM1-AXL/eEF2K signaling axis sensitized GBM cells to TMZ, further enhancing apoptotic and ferroptotic responses. These findings highlight the critical role of the FOXM1-AXL/eEF2K signaling pathway in GBM progression and suggest that targeting this axis may offer a novel multitargeted therapeutic strategy in GBM.

TAM-released factors, such as MCP1, Gas6, and exosomes, induce eEF2K expression in PDAC cells, as well as the activity of AXL, SRC, VEGF, Snail, and MMP2, contributing to epithelial-to-mesenchymal transition (EMT), invasion, metastasis, and angiogenesis. In conclusion, our findings reveal for the first time that eEF2K is a critical oncogenic driver of PDAC tumor growth and thus targeting eEF2K represents a promising and novel therapeutic strategy for PDAC.

Pancreatic ductal adenocarcinoma (PDAC), a highly aggressive malignancy with increasing incidence and low survival rates, urgently requires novel therapeutic strategies to overcome the limitations posed by current treatment agents like gemcitabine...Collectively, these findings identify LHA as a dual-function agent: a natural eEF2K inhibitor and a pyroptosis inducer with potent antitumor activity against PDAC. This study provides a foundational rationale for further clinical exploration of LHA as a promising chemotherapeutic agent or adjuvant to enhance PDAC treatment outcomes.