Molecular Testing and Treatment Strategies in RET-Rearranged NSCLC Patients: Stay on Target to Look Forward

RET alterations are recognized as key oncogenic drivers in different cancer types, including non-small cell lung (NSCLC). Multikinase inhibitors (MKIs) with anti-RET activities resulted variable efficacy significant toxicities because of low target specificity. Selective kinase inhibitors, such pralsetinib and selepercatinib, demonstrated high favorable tolerability advanced RET-rearranged NSCLC patients, leading to their introduction the clinical setting. Among approaches available for identification rearrangements, next-generation sequencing (NGS) assays present substantial advantages terms turnaround time diagnostic accuracy, even if potentially limited by accessibility issues. The recent advent novel effective targeted therapies raises several questions regarding emergence resistance mechanisms potential ways prevent/overcome them. In this review, we discuss molecular testing treatment strategies manage fusion positive patients a focus on future perspectives rapidly evolving scenario.