Advances in Research on the Mechanisms of GABAergic Signaling in Tumors and Its Targeted Intervention Strategies

γ-Aminobutyric acid（GABA） is an important inhibitory neurotransmitter in the nervous system. It not only participates in regulating normal physiological functions but is also associated with the pathogenesis of various diseases, and plays a significant role in multiple tumors, including colorectal cancer, lung cancer, breast cancer, and melanoma. Disorders of GABA metabolism in tumor cells or other cells of the body can lead to alterations in GABA concentration, thereby directly affecting tumor cells, or indirectly regulating tumor progression by affecting the tumor microenvironment and immune cell activity. Studies have shown that by activating GABA type A receptors（GABA_AR） or type B receptors（GABA_BR）, GABA influences key signaling pathways such as calcium pathway, phosphoinositide 3-kinase（PI3K）/protein kinase B（AKT） pathway, cAMP response element-binding protein（CREB） pathway, mitogen-activated protein kinase（MAPK）/extracellular signal-regulated kinase（ERK）/CREB pathway, nuclear factor κB（NF-κB） pathway, and Wnt/β-catenin pathway, ultimately exerting pro-tumorigenic or anti-tumorigenic effects. Intervention in GABAergic signaling pathway has emerged as a promising new direction in the field of cancer therapy. This review summarizes the advances in research on the mechanisms of GABAergic signaling in tumors and its targeted intervention strategies, aiming to provide insights and references for the development of novel anti-tumor drugs.