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Eukaryotic elongation factor 2 kinase is an atypical alpha kinase that plays a key role in protein synthesis by down-regulating the extension step. It achieves this by phosphorylating eukaryotic elongation factor 2 or undergoing self-phosphorylation at multiple sites to inhibit its function in translational elongation. In a few different types of malignancies, studies have found that eEF2K is highly activated or over-expressed. eEF2K inhibits the apoptotic process in cancer possibly by modulating the expression of some apoptotic proteins such as XIAP, PI3KCI and p70S6K. In various forms of cancer, recent research has revealed that eEF2K is significantly activated or over-expressed. By identifying the specific mechanisms through which eEF2K operates to promote tumor growth and survival, it will be able to develop more effective treatments that target this pathway directly. Furthermore, it is possible that eEF2K plays a critical role in the crosstalk between apoptosis and autophagy in cancer. In addition to these exciting findings, there are several conceptual strategies being explored to further refine and enhance the efficacy of these inhibitors. Repurposed drugs, which are already approved for other indications, offer an attractive avenue for expedited clinical translation. Double-targeted drugs that simultaneously target eEF2K and another key signaling pathway could also provide synergistic effects against cancer cells. Furthermore, drug combinations that incorporate multiple eEF2K inhibitors or combine them with other targeted therapies may represent a powerful approach to overcome resistance mechanisms and improve treatment outcomes in various types of cancers. However, there are still significant challenges in designing an ideal targeted drug. This paper discusses some potential inhibitors targeting eEF2K with mechanism of apoptosis and therapeutic potential in the cancer setting. These inspiring discoveries provide some promising methods for inhibiting eEF2K with micro-molecule agents, which may further enhance potential anticancer treatment and its therapeutic level. Overall, these innovative approaches offer new hope for patients battling cancer and highlight the importance of continued research efforts in this field.
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