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Current Oncology Reports
Published in: Current Oncology Reports 2/2019

01-02-2019 | Tyrosine Kinase Inhibitors | Evolving Therapies (RM Bukowski, Section Editor)

TRK Inhibitors: Clinical Development of Larotrectinib

Authors: Munveer S. Bhangoo, Darren Sigal

Published in: Current Oncology Reports | Issue 2/2019

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Abstract

Purpose of Review

In this review, we highlight the pre-clinical development, recent clinical studies, and future directions of larotrectinib in patients with NTRK fusion-positive tumors.

Recent Findings

The tropomyosin receptor kinase family, TrkA, TrkB, and TrkC, transmit extracellular signals via a variety of intracellular pathways to promote normal neuronal development. TrkA, B, and C are encoded by NTRK1, 2, and 3, respectively. NTRK chromosomal alterations, most commonly gene fusions, have been identified as driver mutations in a broad range of malignancies. Small molecule tyrosine kinase inhibitors of Trk, including larotrectinib, have shown broad clinical activity across multiple tumor types with NTRK fusion events.

Summary

Although the prevalence of NTRK alterations is low, the exceptional activity of larotrectinib makes NTRK alterations an important predictive biomarker to screen for in any cancer.
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Metadata
Title
TRK Inhibitors: Clinical Development of Larotrectinib
Authors
Munveer S. Bhangoo
Darren Sigal
Publication date
01-02-2019
Publisher
Springer US
Published in
Current Oncology Reports / Issue 2/2019
Print ISSN: 1523-3790
Electronic ISSN: 1534-6269
DOI
https://doi.org/10.1007/s11912-019-0761-y

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