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Review

NTRK Fusions, from the Diagnostic Algorithm to Innovative Treatment in the Era of Precision Medicine

1
Pathology Unit, Department of Mental and Physic Health and Preventive Medicine, University of Campania ‘Luigi Vanvitelli’ Complesso di Santa Patrizia, Via Luciano Armanni, 580131 Naples, Italy
2
Department of Medical Oncology, Istituto Nazionale Tumori (IRCCS), Centro di Riferimento Oncologico di Aviano, Via Franco Gallini 2, 33081 Aviano (PN) Italy
3
Pathology Unit Department of Pathology, Santobono-Pausilipon Children’s Hospital, Via Posillipo, 80123 Naples, Italy
4
Oncology Unit, Department of Clinical Medicine and Surgery, University of Naples “Federico II”, Via Pansini, 80131 Naples, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(10), 3718; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103718
Received: 17 April 2020 / Revised: 17 May 2020 / Accepted: 21 May 2020 / Published: 25 May 2020
(This article belongs to the Special Issue Tumor Biobanks at the Service of Precision Medicine)
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. View Full-Text
Keywords: neurotrophic tyrosine receptor kinase (NTRK) fusions; NTRK1; NTRK2; NTRK3; ETV6-NTRK3; NGS; FISH; Pan-TRK IHC; tumor biobanks neurotrophic tyrosine receptor kinase (NTRK) fusions; NTRK1; NTRK2; NTRK3; ETV6-NTRK3; NGS; FISH; Pan-TRK IHC; tumor biobanks
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MDPI and ACS Style

Zito Marino, F.; Pagliuca, F.; Ronchi, A.; Cozzolino, I.; Montella, M.; Berretta, M.; Errico, M.E.; Donofrio, V.; Bianco, R.; Franco, R. NTRK Fusions, from the Diagnostic Algorithm to Innovative Treatment in the Era of Precision Medicine. Int. J. Mol. Sci. 2020, 21, 3718. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103718

AMA Style

Zito Marino F, Pagliuca F, Ronchi A, Cozzolino I, Montella M, Berretta M, Errico ME, Donofrio V, Bianco R, Franco R. NTRK Fusions, from the Diagnostic Algorithm to Innovative Treatment in the Era of Precision Medicine. International Journal of Molecular Sciences. 2020; 21(10):3718. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103718

Chicago/Turabian Style

Zito Marino, Federica, Francesca Pagliuca, Andrea Ronchi, Immacolata Cozzolino, Marco Montella, Massimiliano Berretta, Maria E. Errico, Vittoria Donofrio, Roberto Bianco, and Renato Franco. 2020. "NTRK Fusions, from the Diagnostic Algorithm to Innovative Treatment in the Era of Precision Medicine" International Journal of Molecular Sciences 21, no. 10: 3718. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103718

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