Fusion genes ALK, ROS1, and NTRK1/2/3 in pediatric brain tumors

Abstract

Oncogenic fusion genes, including ALK, ROS1, NTRK1, NTRK2, and NTRK3, have been detected in various subtypes of tumor. These genes encode human receptor tyrosine kinases, and promising, molecular-targeted agents have been developed for these fusion genes. Recent studies have revealed these fusion genes in pediatric brain tumors, especially infantile glioma and some very rare histological subtypes. In 2019, NTRK inhibitors were clinically approved for NTRK fusion-positive refractory or relapsed pediatric solid tumors. In this paper, we review the current knowledge of pediatric brain tumors and these targetable fusion genes. To develop better treatment strategies and to further expand the clinical application of molecular-targeted agents, various matters must be assessed, including the clinical and pathological features of cases harboring fusion genes, the appropriate timing and duration of the administration of inhibitors, and the mechanisms of resistance to the inhibitors.