The Evolving Diagnostic and Treatment Landscape of NTRK -Fusion-Driven Pediatric Cancers

AbstractThe neurotrophin receptor tyrosine kinase (NTRK1-3) genes have been identified as key fusion partners in a range of pediatric cancers. In childhood cancers,ETV6-NTRK3 fusions are found in the majority of infantile fibrosarcomas and congenital mesoblastic nephromas.NTRK fusions are also found in mammary analog secretory carcinomas (MASC), secretory breast carcinomas, and with modest frequency in high-grade gliomas in very young children. While there are a range of multi-receptor tyrosine kinase inhibitors that show efficacy against TRK kinases, there are now multiple highly selective TRK inhibitors in clinical evaluation. Entrectinib and larotrectinib have been evaluated in early-phase clinical trials for children and demonstrated high response rates with good durability of response. Both agents are now approved in the United States in an age and histology agnostic manner for children (age  >  12 years for entrectinib; all ages for larotrectinib) for the treatment of solid tumors harboringNTRK fusions without an option for complete surgical resection, with relapsed disease, or without a viable alternative systemic option. More recently, two second-generation TRK inhibitors, selitrectinib and repotrectinib, have been developed and are currently being evaluated in pediatric early phase trials. The Children ’s Oncology Group has also launched a phase II trial of larotrectinib as a neoadjuvant agent for patients with newly diagnosed infantile fi...
Source: Pediatric Drugs - Category: Pediatrics Source Type: research

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