Metabolic reprogramming in cancer: signaling pathways and therapeutic targets

Metabolism is a general term for an ordered series of chemical reactions used to maintain life, and the maintenance of normal cellular activities cannot be separated from metabolism, which is the most basic feature of life. However, metabolic alterations have a dual role. In normal cells, metabolic dysregulation predisposes them to impaired energy acquisition, senescence and even apoptosis. In contrast, metabolic remodeling in tumor cells is advantageous for cancer cell growth and proliferation, driving tumor development and becoming a hallmark of cancer. The inherent heterogeneity and plasticity of many tumor cells themselves are often accompanied by unique alterations in energy metabolism that allow them to survive even in harsh environments where resources are scarce. Notably, tumor cells do not operate in isolation; their metabolic reprogramming is tightly intertwined with metabolic crosstalk and collaborative adaptations involving other components within the tumor microenvironment. Among these metabolic pathways, glycolysis remains the dominant metabolic pathway driving tumor growth and microenvironmental remodeling, even under oxygen-sufficient conditions. Additionally, amino acid, lipid, and polyamine metabolism have been identified as a metabolic regulators that support cancer cell growth, influencing the fate and function of other cells in the microenvironment through metabolite exchange. Targeting cancer metabolism and its interactions with the microenvironment has thus emerged as a promising strategy for treating various malignancies. This article systematically reviews the redistribution of metabolic activities during cancer progression, encompassing both cell-autonomous metabolic reprogramming and microenvironment-mediated metabolic synergy and adaptation. The aim is to provide novel insights and therapeutic strategies for the comprehensive treatment of cancer.