Topoisomerase II Inhibitors in Lung Cancer: A Comprehensive Review of Etoposide's Role and Emerging Therapeutic Strategies

Topoisomerase II inhibitors, particularly etoposide, have long been integral to the treatment of lung cancer, especially small cell lung cancer. This review comprehensively examines the mechanisms of action of etoposide, its clinical efficacy, and its role in current lung cancer treatment regimens. Etoposide exerts its anticancer effects by inducing DNA strand breakages through inhibition of topoisomerase II, leading to cancer cell apoptosis. Despite their widespread use, challenges such as drug resistance, toxicity, and limited efficacy in non-small cell lung cancer have spurred ongoing research on combination therapies and novel drug formulations. Emerging therapeutic strategies include the integration of etoposide with immunotherapy, targeted therapies, and novel drug delivery systems aimed at enhancing the therapeutic window and overcoming drug resistance. This article aims to inform the development of more effective treatment strategies by providing a critical overview of the clinical applications of etoposide and exploring future directions for lung cancer therapy.