Rewiring cancer metabolism: oncogenic signaling pathways and targeted therapeutics

Metabolic reprogramming is a hallmark of cancer, playing a critical role in tumorigenesis by supporting cancer cell survival, proliferation, metastasis, and immune evasion. Oncogenic signaling pathways regulate key metabolic processes by orchestrating gene expression and enhancing metabolic enzyme activity, ensuring cancer cells meet their bioenergetic and biosynthetic demands. Here, we highlight the roles of major oncogenic metabolic signaling pathways, including phosphoinositide 3-kinase (PI3K)/AKT, Myc, p53, and hypoxia-inducible factor (HIF), in driving metabolic rewiring. We provide a conceptual framework to understand why metabolic reprogramming occurs in tumor cells, how metabolic alterations contribute to tumorigenesis, metastasis, and immune evasion, and the therapeutic implications of targeting these metabolic vulnerabilities in cancer.