TRK inhibitor activity and resistance in TRK fusion-positive cancers in adults Journal Article


Authors: Harada, G.; Drilon, A.
Article Title: TRK inhibitor activity and resistance in TRK fusion-positive cancers in adults
Abstract: NTRK fusions drive oncogenesis in a variety of adult cancers. The approval of the first-generation TRK inhibitors, larotrectinib and entrectinib, for any cancer with an NTRK fusion represented a focal point in tumor-agnostic drug development. These agents achieve high response rates and durable disease control, and display intracranial activity. The use of these agents has resulted in a deeper understanding of the clinical consequences of TRK inhibition. These on-target side effects include dizziness, weight gain, and withdrawal pain. The study of TRK inhibitor resistance led to the development of next generation drugs, such as selitrectinib, repotrectinib, taletrectinib, and other agents that maintain disease control against selected acquired kinase domain mutations. This review discusses the clinical efficacy of TRK inhibitors, their safety profiles, and resistance mechanisms with a focus on data in adult cancers. © 2022
Keywords: trk; ntrk gene fusions; trk fusion cancer; trk inhibitors
Journal Title: Cancer Genetics
Volume: 264-265
ISSN: 2210-7762
Publisher: Elsevier Inc.  
Date Published: 2022-06-01
Start Page: 33
End Page: 39
Language: English
DOI: 10.1016/j.cancergen.2022.03.002
PROVIDER: scopus
PUBMED: 35334340
PMCID: PMC9133157
DOI/URL:
Notes: Article -- Export Date: 1 April 2022 -- Source: Scopus
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  1. Alexander Edward Drilon
    633 Drilon
  2. Guilherme Harada
    28 Harada