Multidimensional Regulatory Network and Spatiotemporal Specificity of FOXO Transcription Factors in Digestive System Tumors: Recent Advances

Digestive system malignancies are a globally prevalent type of cancer that severely threatens human health. As pivotal intracellular transcriptional regulators, the forkhead box O (FOXO) protein family plays central roles in diverse physiological and pathological processes, including cell proliferation, apoptosis, and metabolism. Accumulating evidence has verified that FOXO factors exhibit dual functions as both tumor suppressors and oncoproteins. Notably, this functional duality displays a spatiotemporally specific switching pattern according to distinct stages of tumor progression and the physiological characteristics of different digestive system tumors, which poses substantial challenges for FOXO-targeted cancer therapy. Therefore, this review systematically summarizes the molecular mechanisms underlying the functional switching of FOXO in digestive system malignancies from the two dimensions of tumor progression stage and tumor-specific physiological properties, and elaborates the corresponding targeted therapeutic strategies. This work aims to provide a systematic theoretical reference for the precise intervention of digestive system tumors.