The Role of Ion Channels in Cancer Therapy

Ion channels and transporters have recently been identified as key regulators of cancer progression and ion channel blockers as potential drugs to target key hallmarks of cancer including proliferation, migration, and apoptosis. Their disruption in tumor cells provides exclusive therapeutic possibilities to regulate targeted treatments. This review highlights the mechanistic roles of ion channels (e.g., voltage-gated Ca2+/K+ channels, TRP channels) and transporters (e.g., SLCs, ABC pumps) in oncogenesis and explores their potential as druggable targets in precision oncology. Aberrant expression of ion channels like KV10.1 (Eag1) and TRPM8 promotes tumor growth by modulating Ca2+ signaling and membrane potential, while transporters such as GLUT1 and MCT1 sustain metabolic reprogramming in hypoxic microenvironments. Notably, ABC transporters contribute to multidrug resistance (MDR), necessitating novel inhibitors like tariquidar to restore chemosensitivity. Advances in cryo-EM and electrophysiology have enabled structure-guided design of channel blockers (e.g., senicapoc for KCa3.1) and transporter modulators with improved specificity. Challenges include balancing channel inhibition with systemic toxicity and overcoming compensatory mechanisms. Emerging solutions involve RNAi-based silencing and nanocarriers for tumor-selective delivery. The integration of ion channel pharmacogenomics with patient-derived organoid models promises to refine therapeutic stratification. By elucidating the oncogenic roles of ion transport systems, this paradigm opens avenues for innovative combination therapies and repurposing of existing channel drugs—ushering in a new era of electrophysiology-informed cancer treatment.