Novel roles of ammonia in physiology and cancer: Novel roles of ammonia in physiology and cancer

Ammonia, traditionally recognized as a toxic nitrogen waste product, has recently emerged as a significant player in diverse physiological processes and its implications in cancer biology. This review article provides a comprehensive overview of the novel roles of ammonia in physiology and its association with cancer progression. By addressing the multifaceted impact of ammonia on cellular signaling pathways, energy metabolism, and tumor microenvironment dynamics, we examine the intricate interplay between ammonia and key physiological functions, from neurotransmission and metabolic homeostasis to cancer cell proliferation and immune modulation. Notably, ammonia accumulates within tumor microenvironments, promoting non-essential amino acid synthesis, stimulating mTORC1 activation, promoting lipid synthesis, and impairing various immune cell function, thereby promoting tumor progression. Furthermore, the potential dual roles of ammonia as both a tumorigenic factor and a therapeutic target in cancer are discussed, shedding light on its complex regulatory mechanisms and potential clinical implications. This timely review aims to deepen our understanding of the emerging physiological and pathological roles of ammonia, offering valuable insights into its significance as a potential target for diagnostic and therapeutic interventions in cancer and beyond.