AMPK signaling in cancer: Molecular insights and therapeutic opportunities

AMP-activated protein kinase (AMPK) is a highly conserved serine/threonine kinase regarded as an indispensable energy sensor during metabolic stress, coordinating diverse biological processes, including glycolysis, the tricarboxylic acid (TCA) cycle, mitochondrial dynamics, and multiple stress-responsive signaling pathways. Growing evidence shows that dysregulated AMPK signaling plays closely linked roles in tumorigenesis. Depending on the context, AMPK signaling can suppress or promote tumor growth. Mechanistically, dysregulated AMPK kinase activity contributes to metabolic reprogramming, mitochondrial dysfunction, and epigenetic alterations, all recognized hallmarks of cancer. Consequently, targeting AMPK signaling has emerged as a promising strategy for cancer therapy. In this review, we summarize the molecular mechanisms regulating AMPK signaling, discuss its dual functions in tumor biology, highlight recent advances in AMPK-targeted therapeutic strategies, and address current challenges and future perspectives for the clinical translation of AMPK-targeted cancer therapy.