Toxin peptides targeting acid-sensing ion channels: Opportunities for cancer diagnosis and therapy

Acid-sensing ion channels (ASICs) are proton-gated cation channels widely expressed throughout the mammalian nervous system, where they play key roles in processes such as neuronal excitability, synaptic plasticity and pain perception. Their activation by extracellular acidification makes them highly responsive to changes in pH, which have been implicated in numerous pathologies, including cancer, where acidic microenvironments and ion imbalance are hallmark features. In recent years, toxin peptides have emerged as highly selective molecular tools to probe and modulate ASIC activity. These natural ligands not only provide critical insights into ASIC structure and function, but also offer promising leads for diagnostic imaging and targeted therapies. Their specificity and potency make them strong candidates for theranostic strategies, particularly in pathologies characterized by ASIC overexpression or dysfunction. This review highlights the physiological and pathological roles of ASICs, examines the contribution of toxin peptides to ASIC research, and discusses the growing translational potential of ASIC modulation, from biomedical imaging to the development of targeted treatments with a particular focus on oncological applications.