The dual role of AMPK in cancer metabolic reprogramming

Metabolic dysregulation is a core hallmark of tumor cells, which reshapes energy metabolism patterns to meet the demands of rapid proliferation, invasion, metastasis, and drug resistance. AMP‑activated protein kinase (AMPK), as a central regulator of cellular energy homeostasis, senses changes in the intracellular AMP/ATP ratio and extensively participates in the regulation of glucose metabolism, lipid metabolism, amino acid metabolism, and autophagy. In the field of oncology, the role of AMPK is controversial. Initially, because it is associated with liver kinase B1 (LKB1) and exhibits growth‑suppressive effects, AMPK was considered a tumor suppressor. However, recent studies across various cancer types have clearly demonstrated that AMPK possesses pro‑survival activity, thereby promoting tumor progression, particularly under tumor‑associated stress conditions such as hypoxia, nutrient deprivation, and oxidative stress. This review systematically describes the dual role of AMPK in cancer metabolic reprogramming, summarizes the research progress of AMPK‑targeted cancer therapeutic strategies, and discusses the current challenges and future directions, aiming to provide a theoretical reference for optimizing AMPK‑targeted cancer metabolic therapy.