First Report of Entrectinib as a Treatment Option for Pure Squamous Cell Carcinoma Harboring ROS1 Rearrangement: Exploring the Role of Next-Generation Sequencing in Targeted Therapy

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Among the NSCLC subtypes, squamous cell carcinoma (SCC) is less frequently associated with actionable genetic alterations. Herein, we present the first known case of <i>ROS1</i> rearrangement in pure SCC, identified using next-generation sequencing (NGS), and successfully treated with entrectinib for approximately one year. This case highlights the potential of <i>ROS1</i> as a therapeutic target in SCC, which has historically been considered rare, as <i>ROS1</i>-rearranged SCC accounts for only 0.2% according to the Foundation Medicine database. This underscores the importance of incorporating NGS into clinical practice, particularly for never smokers/light smokers or patients with advanced SCC of the lungs, to identify targetable mutations and guide personalized therapy.