The BMAL1–melatonin axis in gastric tumorigenesis and progression: mechanisms and implications

Gastric cancer is a prevalent malignancy with complex pathogenesis. Circadian disruption has emerged as a contributor to tumorigenesis. BMAL1, a core circadian clock gene, and melatonin, a principal rhythm-regulating hormone, are both critical for maintaining physiological homeostasis. This review summarizes their expression changes, biological functions, and potential interactions in gastric cancer. We focus on the molecular mechanisms through which they regulate cell cycle, apoptosis, metabolic reprogramming, DNA damage repair, and the tumor microenvironment, as well as key signaling pathways including Wnt/β-catenin and PI3K/Akt. Based on existing evidence, we propose the “BMAL1–melatonin axis” hypothesis and discuss the prospects of targeted prevention and therapeutic strategies. Notably, direct experimental evidence for their interaction in gastric cancer remains lacking, and future gastric cancer-specific functional studies are urgently needed to validate this hypothesis.