Open Access

REVIEW

Targeting AMPK for Cancer Therapy: Metabolic Reprogramming as a Therapeutic Strategy

Minseo Hong, Jea-Hyun Baek^*

School of Life Science, Handong Global University, Pohang, 37554, Republic of Korea

* Corresponding Author: Jea-Hyun Baek. Email:

Oncology Research 2025, 33(10), 2699-2724. https://doi.org/10.32604/or.2025.067487

Received 05 May 2025; Accepted 05 August 2025; Issue published 26 September 2025

Abstract

AMP-activated protein kinase (AMPK) is a highly conserved serine/threonine kinase that functions as a central regulator of cellular energy status. In cancer, where metabolic reprogramming enables rapid proliferation and survival under stress, AMPK functions as a metabolic checkpoint that restrains tumor growth by inhibiting biosynthetic pathways and promoting catabolic processes, such as autophagy and fatty acid oxidation. Given its role in opposing many hallmarks of cancer metabolism, AMPK has attracted significant interest as a therapeutic target. This review examines the molecular mechanisms by which AMPK influences tumor progression and evaluates the preclinical and clinical evidence for pharmacological AMPK activation using agents such as metformin, phenformin, and canagliflozin. While promising anti-tumor effects have been reported in specific contexts—such as HER2-positive breast cancer, colorectal cancer, and metabolically distinct lung cancer subtypes—clinical efficacy remains variable. Limitations include indirect activation mechanisms, low tissue penetrance, tumor heterogeneity, and lack of reliable biomarkers for patient selection. We discuss emerging strategies to overcome these challenges, including combination therapies, metabolic stratification, and the development of direct AMPK activators or mRNA-based delivery platforms. Together, these insights support a renewed focus on AMPK as a modifiable node in cancer metabolism and a candidate for integration into precision oncology frameworks.

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Keywords

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