NTRK-Targeted Therapy in Lung Cancer

Xiaoliang Wu, Lin Zhu, Patrick C. Ma

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Gene rearrangements or fusions as a tumorigenic genomic driver event have been identified as a common recurrent occurrence in a variety of human malignancies. The neurotrophic tyrosine receptor kinase gene family contains NTRK1, NTRK2, and NTRK3, which encode the proteins tropomyosin receptor kinase A, B, and C (TRKA, TRKB, TRKC), respectively. TRKA, TRKB, and TRKC can be activated by the specific ligands, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT3). Interestingly, although NTRK gene fusions occur relatively rarely in human cancers overall, they have been found to be present broadly in many different tumor types, including both pediatric and adult malignancies. The recognition of NTRK fusions as driver genomic event in recent years have prompted impactful clinical therapeutic development which demonstrated the efficacy and safety of TRK inhibitors, with a recent approval of larotrectinib by the US Food and Drug Administration in a cancer-agnostic manner for NTRK fusion-positive cancers. Here, we reviewed the biology of NTRK gene fusions, antitumor activity of TRK inhibitors, clinical trials development, and challenges and future perspectives of NTRK-targeted therapies in human cancer with a special focus on lung cancer.

Original languageEnglish (US)
Title of host publicationCurrent Cancer Research
PublisherSpringer Nature
Pages137-161
Number of pages25
DOIs
StatePublished - 2019

Publication series

NameCurrent Cancer Research
ISSN (Print)2199-2584
ISSN (Electronic)2199-2592

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

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