Mechanisms and management of crizotinib-induced toxicity in non-small cell lung cancer

Crizotinib, a first-in-class ALK/ROS1/MET inhibitor, has been shown to significantly improve outcomes in advanced non-small cell lung cancer (NSCLC); however, its clinical utility remains limited by multisystem toxicities. This review synthesizes evidence regarding crizotinib-induced adverse effects-such as hepatotoxicity, cardiotoxicity, and interstitial lung disease-along with associated clinical management strategies. Through a systematic examination of the molecular mechanisms and multifactorial determinants of toxicity, this work aims to enhance understanding of the limitations associated with crizotinib's clinical applicability. Although most toxicities are manageable through dose adjustments, prophylactic monitoring, and adjunct therapies, unresolved mechanistic questions and rare, severe adverse events underscore the need for further research. By integrating molecular insights with practical approaches, this review underscores the essential balance between therapeutic efficacy and toxicity risks, thereby informing personalized treatment decisions and facilitating the development of safer targeted therapies. The synthesis of current knowledge is intended to optimize the clinical application of crizotinib and to foster innovative strategies for toxicity management within the evolving paradigms of NSCLC treatment.