Ntrk fusions, from the diagnostic algorithm to innovative treatment in the era of precision medicine

Federica Zito Marino, Francesca Pagliuca, Andrea Ronchi, Immacolata Cozzolino, Marco Montella, Massimiliano Berretta, Maria Elena Errico, Vittoria Donofrio, Roberto Bianco, Renato Franco

Research output: Contribution to journalReview articlepeer-review

Abstract

In the era of precision medicine, the identification of several predictive biomarkers and the development of innovative therapies have dramatically increased the request of tests to identify specific targets on cytological or histological samples, revolutionizing the management of the tumoral biomaterials. The Food and Drug Administration (FDA) has recently approved a selective neurotrophic tyrosine receptor kinase (NTRK) inhibitor, larotrectinib. Contemporarily, the development of multi-kinase inhibitors with activity in tumors carrying TRK fusions is ongoing. Chromosomal translocations involving the NTRK1, NTRK2, and NTRK3 genes result in constitutive activation and aberrant expression of TRK kinases in numerous cancer types. In this context, the identification of tumors harboring TRK fusions is crucial. Several methods of detection are currently available. We revise the advantages and disadvantages of different techniques used for identifying TRK alterations, including immunohistochemistry, fluorescence in situ hybridization, reverse transcriptase polymerase chain reaction, and next generation sequencing-based approaches. Finally, we propose a diagnostic algorithm based on histology and the relative frequency of TRK fusions in each specific tumor, considering also the economic feasibility in the clinical practice.

Original languageEnglish
Article number3718
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume21
Issue number10
DOIs
Publication statusPublished - May 2 2020

Keywords

  • ETV6-NTRK3
  • FISH
  • Neurotrophic tyrosine receptor kinase (NTRK) fusions
  • NGS
  • NTRK1
  • NTRK2
  • NTRK3
  • Pan-TRK IHC
  • Tumor biobanks

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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