Targeting ion channels: innovative approaches to combat cancer drug resistance

Ion channels, as functional molecules that regulate the flow of ions across cell membranes, have emerged as a promising target in cancer therapy due to their pivotal roles in cell proliferation, metastasis, apoptosis, drug resistance, and so on. Recently, increasing evidence suggests that dysregulation of ion channels is a common characteristic of cancer cells, contributing to their survival and the resistance to conventional therapies. For example, the aberrant expression of sodium (Na⁺) and potassium ion (K⁺) channels is significantly correlated with the sensitivity of chemotherapy drugs. The endogenous calcium (Ca²⁺) channels contribute to the acquired resistance of osimertinib in epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer cell lines. Ferrous ions (Fe²⁺) enhance the sensitivity of breast cancer cells to doxorubicin treatment. Preclinical models have also demonstrated the effect of specific ion channel blockers or modulators on anticancer drug resistance. This review describes the current understanding about the interaction between ion channels and the therapeutic efficacy of anticancer drugs. Then, the therapeutic potential of ion channel blockers or modulators in enhancing the sensitivity or overcoming the resistance of cancer cells to anticancer therapies is discussed. Targeting ion channels will hopefully offer a novel and promising strategy for overcoming cancer drug resistance.