Additionally, except for conditions with pathological characteristics of microvascular proliferation or necrosis, astrocytomas with epidermal growth factor receptor (EGFR) amplification, combined whole chromosome 7 gain and whole chromosome 10 loss (+7/−10), or telomerase reverse transcriptase (TERT) promoter mutation should be diagnosed as GBM ( 3). Recently, the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) recommended that GBM with IDH mutations should be referred to as IDH-mutant astrocytoma and excluded from GBM diagnosis ( 2). The morbidity of GBM increases positively with age, and the median age of patients is 65 years old ( 1). Glioblastoma multiforme (GBM) is the most common primary malignant tumor of the central nervous system (CNS) and accounts for 48% of CNS malignancies, with a morbidity of 3.22 per 100,000 people. More clinical data and future clinical trials are needed to provide more evidence that supports targeted therapy for GBM with NTRK fusions. However, whether NTRK gene fusions can affect survival status, the efficacy and resistance of TRK inhibitors in GBMs are lacking high-level evidences.Ĭonclusions: For GBM patients, NTRK fusions and TRK inhibitors are potential target therapy strategy but remain biological mechanism and clinical significance unclarified. Tropomyosin receptor kinase (TRK) inhibitors have shown efficacy as targeted therapies for extracranial tumors with NTRK fusions in recent clinical trials, with potential CNS tolerability and activity. Results: Several NTRK1/2/3 fusions have been reported in GBM and preclinical studies have proven that NTRK fusions are potential driver mutations in some high-grade gliomas. Methods: We have reviewed the preclinical and clinical evidence for NTRK fusions and TRK inhibitors therapy in cancers with NTRK fusions in pan-cancer and gliomas. Based on multiomics studies, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), BRAF V600E mutation, neurotrophic tyrosine receptor kinase (NTRK) fusions and other potential therapy targets have been found.

Predictive biomarkers, such as methylation of the promoter region of the O6-methylguanine DNA methyltransferase (MGMT) gene, can successfully distinguish subgroups with different prognosis after temozolomide chemotherapy. The standard treatment for GBM is neurosurgical resection, followed by radiochemotherapy and adjuvant temozolomide chemotherapy. Introduction: Glioblastoma multiforme (GBM) is the most common primary central nervous (CNS) system malignancy with a poor prognosis. Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.Yuekun Wang †, Piaopiao Long †, Yu Wang * and Wenbin Ma *

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