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Updated: Jun 20, 2026

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

On Trk--the TrkB signal transduction pathway is an increasingly important target in cancer biology

Carol J Thiele1, Zhijie Li, Amy E McKee

  • 1Cell and Molecular Biology Section, Pediatric Oncology Branch, Center for Cancer Research, CRC, NCI, Bethesda, Maryland 20892, USA. ct47a@nih.gov

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|September 17, 2009
PubMed

Insights

Neurotrophin receptor (Trk) signaling, initially an oncogene, is now vital in neurobiology and nonneuronal cells. Trk inhibitors show promise for various cancers, with combination therapies potentially enhancing efficacy.

Area of Science:

  • Oncology
  • Neurobiology
  • Molecular Biology

Background:

  • Neurotrophin receptor (Trk) signaling, initially recognized as an oncogene, plays a crucial role in neurobiology.
  • Trk signaling is now understood to regulate nonneuronal cell processes and contribute to various cancers beyond neural origins.

Purpose of the Study:

  • To review the multifaceted roles of Trk signaling in both neuronal and nonneuronal cells.
  • To highlight the involvement of Trk signaling in the pathogenesis of diverse human tumors.
  • To discuss the therapeutic potential of Trk inhibitors in cancer treatment.

Main Methods:

  • Literature review of studies on Neurotrophin-Trk signaling.
  • Analysis of Trk expression patterns in different cancer types, including neuroblastoma.
  • Examination of the impact of Brain-derived neurotrophic factor (BDNF)/TrkB pathway activation on tumor characteristics.

Main Results:

  • TrkA expression correlates with good prognosis in neuroblastoma, while TrkB and BDNF expression indicate poor prognosis.
  • Activation of the BDNF/TrkB pathway promotes tumor cell survival, angiogenesis, and resistance to therapies.
  • Trk mutations are sporadic but TrkB expression is linked to tumor pathology.

Conclusions:

  • Trk signaling is a significant factor in tumorigenesis across various cancer types.
  • Targeting Trk signaling with small molecule inhibitors represents a promising therapeutic strategy.
  • Combination therapies involving Trk inhibitors may offer enhanced efficacy in clinical settings.

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