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NTRK Fusions in Sarcomas: Diagnostic Challenges and Clinical Aspects

Tropomyosin receptor kinase (TK) is encoded by the neurotrophic tyrosine receptor kinase genes (NTRK) 1, 2, and 3, whose activation plays an important role in cell cycle proliferation and survival. Fusions of one of these genes can lead to constitutive activation of TRK, which can potentially be onc...

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Autores principales: Siozopoulou, Vasiliki, Smits, Evelien, De Winne, Koen, Marcq, Elly, Pauwels, Patrick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000177/
https://www.ncbi.nlm.nih.gov/pubmed/33803146
http://dx.doi.org/10.3390/diagnostics11030478
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author Siozopoulou, Vasiliki
Smits, Evelien
De Winne, Koen
Marcq, Elly
Pauwels, Patrick
author_facet Siozopoulou, Vasiliki
Smits, Evelien
De Winne, Koen
Marcq, Elly
Pauwels, Patrick
author_sort Siozopoulou, Vasiliki
collection PubMed
description Tropomyosin receptor kinase (TK) is encoded by the neurotrophic tyrosine receptor kinase genes (NTRK) 1, 2, and 3, whose activation plays an important role in cell cycle proliferation and survival. Fusions of one of these genes can lead to constitutive activation of TRK, which can potentially be oncogenic. NTRK fusions are commonly present in rare histologic tumor types. Among sarcomas, infantile fibrosarcoma shows NTRK fusion in more than 90% of the cases. Many other sarcoma types are also investigated for NTRK fusions. These fusions are druggable alteration of the agnostic type, meaning that all NTRK fused tumors can be treated with NTRK-inhibitors regardless of tumor type or tissue of origin. TRK-inhibitors have shown good response rates, with durable effects and limited side effects. Resistance to therapy will eventually occur in some cases, wherefore the next-generation TRK-inhibitors are introduced. The diagnosis of NTRK fused tumors, among them sarcomas, remains an issue, as many algorithms but no guidelines exist to date. Given the importance of this diagnosis, in this paper we aim to (1) analyze the histopathological features of sarcomas that correlate more often with NTRK fusions, (2) give an overview of the TRK-inhibitors and the problems that arise from resistance to the therapy, and (3) discuss the diagnostic algorithms of NTRK fused tumors with emphasis on sarcomas.
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spelling pubmed-80001772021-03-28 NTRK Fusions in Sarcomas: Diagnostic Challenges and Clinical Aspects Siozopoulou, Vasiliki Smits, Evelien De Winne, Koen Marcq, Elly Pauwels, Patrick Diagnostics (Basel) Review Tropomyosin receptor kinase (TK) is encoded by the neurotrophic tyrosine receptor kinase genes (NTRK) 1, 2, and 3, whose activation plays an important role in cell cycle proliferation and survival. Fusions of one of these genes can lead to constitutive activation of TRK, which can potentially be oncogenic. NTRK fusions are commonly present in rare histologic tumor types. Among sarcomas, infantile fibrosarcoma shows NTRK fusion in more than 90% of the cases. Many other sarcoma types are also investigated for NTRK fusions. These fusions are druggable alteration of the agnostic type, meaning that all NTRK fused tumors can be treated with NTRK-inhibitors regardless of tumor type or tissue of origin. TRK-inhibitors have shown good response rates, with durable effects and limited side effects. Resistance to therapy will eventually occur in some cases, wherefore the next-generation TRK-inhibitors are introduced. The diagnosis of NTRK fused tumors, among them sarcomas, remains an issue, as many algorithms but no guidelines exist to date. Given the importance of this diagnosis, in this paper we aim to (1) analyze the histopathological features of sarcomas that correlate more often with NTRK fusions, (2) give an overview of the TRK-inhibitors and the problems that arise from resistance to the therapy, and (3) discuss the diagnostic algorithms of NTRK fused tumors with emphasis on sarcomas. MDPI 2021-03-09 /pmc/articles/PMC8000177/ /pubmed/33803146 http://dx.doi.org/10.3390/diagnostics11030478 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Review
Siozopoulou, Vasiliki
Smits, Evelien
De Winne, Koen
Marcq, Elly
Pauwels, Patrick
NTRK Fusions in Sarcomas: Diagnostic Challenges and Clinical Aspects
title NTRK Fusions in Sarcomas: Diagnostic Challenges and Clinical Aspects
title_full NTRK Fusions in Sarcomas: Diagnostic Challenges and Clinical Aspects
title_fullStr NTRK Fusions in Sarcomas: Diagnostic Challenges and Clinical Aspects
title_full_unstemmed NTRK Fusions in Sarcomas: Diagnostic Challenges and Clinical Aspects
title_short NTRK Fusions in Sarcomas: Diagnostic Challenges and Clinical Aspects
title_sort ntrk fusions in sarcomas: diagnostic challenges and clinical aspects
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000177/
https://www.ncbi.nlm.nih.gov/pubmed/33803146
http://dx.doi.org/10.3390/diagnostics11030478
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