Medical Services

ROS1-rearranged non-small cell lung cancer (NSCLC) is a distinct molecular subtype occurring in approximately 1–2% of NSCLC patients, primarily those with adenocarcinoma histology. It is more frequently seen in younger patients and those with a light or no smoking history. ROS1 rearrangements result in the production of abnormal fusion proteins that activate oncogenic signaling pathways such as PI3K/AKT, MAPK/ERK, and JAK/STAT3, driving tumor growth.

Diagnosis typically involves molecular testing techniques like fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS) to identify ROS1 gene fusions. Targeted therapy against ROS1 has significantly transformed treatment paradigms, with several tyrosine kinase inhibitors (TKIs) such as crizotinib, entrectinib, and repotrectinib approved for first-line treatment in the metastatic setting. These therapies have shown high response rates (60–80%) and prolonged progression-free survival compared to conventional chemotherapy.

Despite initial success, resistance to ROS1 TKIs often develops, prompting the development of next-generation inhibitors with improved central nervous system penetration and broader resistance mutation coverage. ROS1-rearranged NSCLC patients tend to have better overall survival compared to other molecular subtypes, especially when treated with targeted therapies. Ongoing research aims to optimize treatment sequencing, overcome resistance, and extend benefits to earlier-stage disease.