Harnessing the ion transportome to treat cancer

Abstract Despite significant advances in early detection and therapeutic opportunities, cancer remains a critical global health challenge. The greatest barrier to reducing cancer‐associated mortality is the persistent problem of therapeutic resistance and metastasis. Standard treatment approaches, including surgery combined with chemotherapy and radiation, are effective for many patients with localised disease. However, a substantial proportion of patients will experience recurrence and therapy resistance, leading to treatment failure and poor outcomes. This adverse prognosis for patients highlights the critical need to identify new therapeutic targets capable of improving long‐term survival. The ion transportome comprises ion channels, solute transporters and pumps that regulate controlled movement of sodium (Na + ), potassium (K + ), calcium (Ca 2+ ), chloride (Cl − ) and hydrogen (H + ) across cell membranes. Ion transport is central to many cellular processes, including cell growth, volume regulation, proliferation and migration. In many solid tumours, the finely tuned ionic balance becomes dysregulated, with aberrant expression or activity of membrane transport proteins being closely linked to many of the hallmarks of cancer. Ion channel modulation using pharmacological agents designed to treat channelopathies has demonstrated promise in suppressing cancer progression in preclinical models. Thus, targeting ion‐driven vulnerabilities within solid tumours may complement existing therapies to overcome resistance and improve patient outcomes. The dynamic nature of ion transport mechanisms means that addressing critical research questions regarding their suitability as pharmacological targets is challenging, highlighting the need to develop innovative approaches to study these processes in oncology. image