Novel SNX25-ROS1 fusion mutation confers therapeutic sensitivity to entrectinib: a case report and literature review

ROS1 gene fusions are oncogenic driver in 1-2% non-small cell lung cancer (NSCLC). This report presents the first case of a novel SNX25-ROS1 fusion mutation in a 56-year-old female with lung adenocacinoma, presenting with headaches and behavioral changes. Imaging revealed a primary tumor in the lung and metastasis to lymph nodes, brain, and bones. Histopathological examination confirmed the diagnosis of lung adenocarcinoma, classified as cT3N3M1 (Stage IV). Next-generation sequencing identified a previously unreported SNX25-ROS1 fusion mutation. A fusion was identified in exon 1 of the SNX25 gene and exon 31 of the ROS1 gene. The fusion occurs within ROS1 intron 31, and the complete kinase domain is retained. Based on this finding, the patient was initiated on targeted therapy with entrectinib. Follow-up imaging at six months demonstrated significant reduction in the primary lung tumor size, regression of metastatic lesions, and resolution of intracranial edema. The patient exhibited marked clinical improvement with no significant treatment-related adverse events. This case report identifies a novel SNX25-ROS1 fusion mutation in NSCLC, showing strong sensitivity to ROS1-targeted therapy. It highlights the importance of molecular profiling in detecting rare genetic alterations and underscores the therapeutic potential of targeted treatments for NSCLC with unique molecular subtypes.