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Review
. 2021 Mar;81(4):445-452.
doi: 10.1007/s40265-020-01459-w.

Detecting and Targeting NTRK Fusions in Cancer in the Era of Tumor Agnostic Oncology

Kristoffer S Rohrberg  1 , Ulrik Lassen  2
Affiliations
Review

Detecting and Targeting NTRK Fusions in Cancer in the Era of Tumor Agnostic Oncology

Kristoffer S Rohrberg et al. Drugs. 2021 Mar.

Abstract

Gene rearrangements involving the neurotrophic receptor kinase genes NTRK1, NTRK2, and NTRK3 (referred to as TRK, encoding TRKA, TRKB, and TRKC, respectively) result in highly oncogenic fusions. TRK fusions are rare, with a prevalence of < 1% in solid tumors. Detection of TRK fusions can be based on fluorescence in-situ hybridization (FISH), immunohistochemistry (IHC), and next-generation sequencing (NGS), where RNA sequencing is the most sensitive method. Inhibition of TRK fusions with highly selective small-molecule TRK inhibitors (TRKi) such as entrectinib and larotrectinib, results in profound responses in most cancer patients, regardless of cancer histology. Even response in CNS metastases is relatively common. Although responses are often durable, many patients develop resistance to TRKi due to mutations in one of the TRK genes, or due to genetic alterations conferring activation of alternative oncogenic signaling pathways. Second-generation TRKi have been developed, which can overcome some of the TRK resistance mutations. TRKi are well tolerated, with most common adverse events being related to on-target/off-tumor inhibition of TRKs.

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References

    1. Dienstmann R, Rodon J, Barretina J, Tabernero J. Genomic medicine frontier in human solid tumors: prospects and challenges. J Clin Oncol. 2013;31:1874–84. - PubMed
    1. Garraway LA. Genomics-driven oncology: framework for an emerging paradigm. J Clin Oncol. 2013;31:1806–14. - PubMed
    1. Macconaill LE, Garraway LA. Clinical implications of the cancer genome. J Clin Oncol. 2010;28:5219–28. - PubMed - PMC
    1. Meador CB, Micheel CM, Levy MA, Lovly CM, Horn L, Warner JL, et al. Beyond histology: translating tumor genotypes into clinically effective targeted therapies. Clin Cancer Res. 2014;20:2264–75. - PubMed - PMC
    1. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344:1031–7. - PubMed

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