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  • Title: Larotrectinib, a selective tropomyosin receptor kinase inhibitor for adult and pediatric tropomyosin receptor kinase fusion cancers.
    Author: Farago AF, Demetri GD.
    Journal: Future Oncol; 2020 Mar; 16(9):417-425. PubMed ID: 32129093.
    Abstract:
    Gene fusions involving NTRK1, NTRK2 and NTRK3 are oncogenic drivers across a wide variety of cancer types. Inhibitors of the chimeric TRKA/B/C protein kinases encoded by these fusions are now available, including larotrectinib, a potent and highly selective oral drug. Integrated data from three trials demonstrate substantial clinical activity of larotrectinib in patients with many different types of cancers harboring NTRK fusions. Larotrectinib has received accelerated approval from both the US FDA and the EMA. Resistance mutations have been observed in the kinase domains of the NTRK fusion genes and development of next-generation tropomyosin receptor kinase inhibitors designed to overcome such resistance mutations is being actively pursued in clinical trials and ongoing drug discovery efforts.
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