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TRK Inhibitors: Clinical Development of Larotrectinib

  • Evolving Therapies (RM Bukowski, Section Editor)
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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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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Correspondence to Darren Sigal.

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Munveer S. Bhangoo declares that he has no conflict of interest.

Darren Sigal has a patent issued on a method of treating neuroendocrine tumors.

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Bhangoo, M.S., Sigal, D. TRK Inhibitors: Clinical Development of Larotrectinib. Curr Oncol Rep 21, 14 (2019). https://doi.org/10.1007/s11912-019-0761-y

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