AUTHOR=Cipri Selene , Fabozzi Francesco , Del Baldo Giada , Milano Giuseppe Maria , Boccuto Luigi , Carai Andrea , Mastronuzzi Angela 

TITLE=Targeted therapy for pediatric central nervous system tumors harboring mutagenic tropomyosin receptor kinases

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1235794

DOI=10.3389/fonc.2023.1235794

ISSN=2234-943X

ABSTRACT=<p>The family of the neurotrophic tyrosine kinase receptor (<italic>NTRK</italic>) gene encodes for members of the tropomyosin receptor kinase (TRK) family. Rearrangements involving <italic>NTRK1/2/3</italic> are rare oncogenic factors reported with variable frequencies in an extensive range of cancers in pediatrics and adult populations, although they are more common in the former than in the latter. The alterations in these genes are causative of the constitutive activation of TRKs that drive carcinogenesis. In 2017, first-generation TRK inhibitor (TRKi) larotrectinib was granted accelerated approval from the FDA, having demonstrated histologic-agnostic activity against <italic>NTRK</italic>s fusions tumors. Since this new era has begun, resistance to first-generation TRKi has been described and has opened the development of second-generation molecules, such as selitrectinib and repotrectinib. In this review, we provide a brief overview of the studies on <italic>NTRK</italic> alterations found in pediatric central nervous system tumors and first and second-generation TRKi useful in clinical practice.</p>