Targeting Ion Channels for Cancer Therapy: From Pathophysiological Mechanisms to Clinical Translation.

Cancer remains a major global health burden, representing one of the leading causes of mortality among noncommunicable diseases worldwide. Although conventional treatment modalities, including surgical resection, chemotherapy, radiotherapy, targeted therapy, and immunotherapeutic interventions, have demonstrated clinical benefits, their therapeutic efficacy is often constrained by inherent limitations such as low specificity, systemic toxicity, or tumor heterogeneity. These challenges underscore the imperative for developing innovative treatment strategies. Emerging evidence has implicated ion channels as critical players in oncogenesis and cancer progression. These proteins modulate diverse oncogenic phenotypes, including uncontrolled proliferation, metastatic dissemination, and apoptotic resistance. Their frequent dysregulation in malignancies correlates with disease aggressiveness and clinical outcomes, positioning them as promising targets for precision oncology. Notably, pharmacological modulation of ion channels exerts multifaceted antitumor effects, with several channel-targeting agents advancing through clinical trials. This review explores recent advances in ion channel-targeted therapies, emphasizing their mechanisms, clinical applications, and challenges. Furthermore, we examine the pathophysiological contributions of ion channels to tumor biology and evaluate their emerging utility as predictive biomarkers, providing perspectives on addressing critical gaps in current oncologic management.