Unravelling the oncogenic role of eukaryotic elongation factor 2 kinase: A revisited review from underlying mechanisms to targeted therapy

Oct 2, 2025International journal of biological macromolecules

Understanding how eukaryotic elongation factor 2 kinase may promote cancer and its potential as a treatment target

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Abstract

Eukaryotic elongation factor 2 kinase (eEF2K) is overexpressed in various tumor tissues and is associated with tumor growth and metastasis.

eEF2K is a member of the α-kinase family and relies on calcium ions and calmodulin for its activity.
Key signaling pathways that regulate eEF2K include mTORC1-p70S6K-eEF2K and AMPK/eEF2K pathways.
eEF2K influences multiple aspects of cancer biology, including tumor progression, metastasis, and metabolic processes.
Small-molecule inhibitors targeting eEF2K show potential for treating breast and lung cancers.
Emerging therapeutic technologies, such as proteolysis-targeting chimaeras and non-coding RNAs, may enhance cancer treatment strategies.

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Eukaryotic elongation factor 2 kinase (eEF2K), encoded by the human eEF2K gene, belongs to the "α-kinase" family of atypical protein kinases and requires calcium ions and calmodulin (CaM) for its activity. It is overexpressed in various tumor tissues and plays a crucial role in promoting tumor growth, invasion, and metastasis. Consequently, eEF2K is considered a viable target for potential cancer therapies. This review aims to summarize the key signaling pathways that modulate eEF2K activity in tumors, including the mammalian target of rapamycin complex 1 (mTORC1)-the 70 kDa ribosomal protein S6 kinase (p70S6K)-eEF2K and adenosine monophosphate-activated protein kinase (AMPK)/eEF2K pathways. Furthermore, we explore the complex interactions between eEF2K and various aspects of cancer biology, such as cancer progression, metastasis, metabolism, autophagy, and therapeutic response. The therapeutic potential of small-molecule inhibitors targeting eEF2K is highlighted, particularly in the context of breast cancer, lung cancer, and other cancer types. 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.

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Unravelling the oncogenic role of eukaryotic elongation factor 2 kinase: A revisited review from underlying mechanisms to targeted therapy

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