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Sensitivity to Entrectinib Associated With a Novel LMNA-NTRK1 Gene Fusion in Metastatic Colorectal Cancer
In metastatic colorectal cancer (CRC), actionable genetic lesions represent potential clinical opportunities. NTRK1, 2, and 3 gene rearrangements encode oncogenic fusions of the tropomyosin-receptor kinase (TRK) family of receptor tyrosine kinases in different tumor types. The TPM3-NTRK1 rearrangeme...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712682/ https://www.ncbi.nlm.nih.gov/pubmed/26563355 http://dx.doi.org/10.1093/jnci/djv306 |
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author | Sartore-Bianchi, Andrea Ardini, Elena Bosotti, Roberta Amatu, Alessio Valtorta, Emanuele Somaschini, Alessio Raddrizzani, Laura Palmeri, Laura Banfi, Patrizia Bonazzina, Erica Misale, Sandra Marrapese, Giovanna Leone, Antonella Alzani, Rachele Luo, David Hornby, Zachary Lim, Jonathan Veronese, Silvio Vanzulli, Angelo Bardelli, Alberto Martignoni, Marcella Davite, Cristina Galvani, Arturo Isacchi, Antonella Siena, Salvatore |
author_facet | Sartore-Bianchi, Andrea Ardini, Elena Bosotti, Roberta Amatu, Alessio Valtorta, Emanuele Somaschini, Alessio Raddrizzani, Laura Palmeri, Laura Banfi, Patrizia Bonazzina, Erica Misale, Sandra Marrapese, Giovanna Leone, Antonella Alzani, Rachele Luo, David Hornby, Zachary Lim, Jonathan Veronese, Silvio Vanzulli, Angelo Bardelli, Alberto Martignoni, Marcella Davite, Cristina Galvani, Arturo Isacchi, Antonella Siena, Salvatore |
author_sort | Sartore-Bianchi, Andrea |
collection | PubMed |
description | In metastatic colorectal cancer (CRC), actionable genetic lesions represent potential clinical opportunities. NTRK1, 2, and 3 gene rearrangements encode oncogenic fusions of the tropomyosin-receptor kinase (TRK) family of receptor tyrosine kinases in different tumor types. The TPM3-NTRK1 rearrangement is a recurring event in CRC that renders tumors sensitive to TRKA kinase inhibitors in preclinical models. We identified abnormal expression of the TRKA protein in tumor and liver metastases of a CRC patient refractory to standard therapy. Molecular characterization unveiled a novel LMNA-NTRK1 rearrangement within chromosome 1 with oncogenic potential, and the patient was treated with the pan-TRK inhibitor entrectinib, achieving partial response with decrease in hepatic target lesions from 6.8 and 8.2cm in longest diameter to 4.7 and 4.3cm, respectively. To our knowledge, this is the first clinical evidence of efficacy for therapeutic inhibition of TRKA in a solid tumor, illuminating a genomic-driven strategy to identify CRCs reliant on this oncogene to be clinically targeted with entrectinib. |
format | Online Article Text |
id | pubmed-4712682 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-47126822016-01-19 Sensitivity to Entrectinib Associated With a Novel LMNA-NTRK1 Gene Fusion in Metastatic Colorectal Cancer Sartore-Bianchi, Andrea Ardini, Elena Bosotti, Roberta Amatu, Alessio Valtorta, Emanuele Somaschini, Alessio Raddrizzani, Laura Palmeri, Laura Banfi, Patrizia Bonazzina, Erica Misale, Sandra Marrapese, Giovanna Leone, Antonella Alzani, Rachele Luo, David Hornby, Zachary Lim, Jonathan Veronese, Silvio Vanzulli, Angelo Bardelli, Alberto Martignoni, Marcella Davite, Cristina Galvani, Arturo Isacchi, Antonella Siena, Salvatore J Natl Cancer Inst Brief Communication In metastatic colorectal cancer (CRC), actionable genetic lesions represent potential clinical opportunities. NTRK1, 2, and 3 gene rearrangements encode oncogenic fusions of the tropomyosin-receptor kinase (TRK) family of receptor tyrosine kinases in different tumor types. The TPM3-NTRK1 rearrangement is a recurring event in CRC that renders tumors sensitive to TRKA kinase inhibitors in preclinical models. We identified abnormal expression of the TRKA protein in tumor and liver metastases of a CRC patient refractory to standard therapy. Molecular characterization unveiled a novel LMNA-NTRK1 rearrangement within chromosome 1 with oncogenic potential, and the patient was treated with the pan-TRK inhibitor entrectinib, achieving partial response with decrease in hepatic target lesions from 6.8 and 8.2cm in longest diameter to 4.7 and 4.3cm, respectively. To our knowledge, this is the first clinical evidence of efficacy for therapeutic inhibition of TRKA in a solid tumor, illuminating a genomic-driven strategy to identify CRCs reliant on this oncogene to be clinically targeted with entrectinib. Oxford University Press 2015-11-12 /pmc/articles/PMC4712682/ /pubmed/26563355 http://dx.doi.org/10.1093/jnci/djv306 Text en © The Author 2015. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Brief Communication Sartore-Bianchi, Andrea Ardini, Elena Bosotti, Roberta Amatu, Alessio Valtorta, Emanuele Somaschini, Alessio Raddrizzani, Laura Palmeri, Laura Banfi, Patrizia Bonazzina, Erica Misale, Sandra Marrapese, Giovanna Leone, Antonella Alzani, Rachele Luo, David Hornby, Zachary Lim, Jonathan Veronese, Silvio Vanzulli, Angelo Bardelli, Alberto Martignoni, Marcella Davite, Cristina Galvani, Arturo Isacchi, Antonella Siena, Salvatore Sensitivity to Entrectinib Associated With a Novel LMNA-NTRK1 Gene Fusion in Metastatic Colorectal Cancer |
title | Sensitivity to Entrectinib Associated With a Novel LMNA-NTRK1 Gene Fusion in Metastatic Colorectal Cancer |
title_full | Sensitivity to Entrectinib Associated With a Novel LMNA-NTRK1 Gene Fusion in Metastatic Colorectal Cancer |
title_fullStr | Sensitivity to Entrectinib Associated With a Novel LMNA-NTRK1 Gene Fusion in Metastatic Colorectal Cancer |
title_full_unstemmed | Sensitivity to Entrectinib Associated With a Novel LMNA-NTRK1 Gene Fusion in Metastatic Colorectal Cancer |
title_short | Sensitivity to Entrectinib Associated With a Novel LMNA-NTRK1 Gene Fusion in Metastatic Colorectal Cancer |
title_sort | sensitivity to entrectinib associated with a novel lmna-ntrk1 gene fusion in metastatic colorectal cancer |
topic | Brief Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712682/ https://www.ncbi.nlm.nih.gov/pubmed/26563355 http://dx.doi.org/10.1093/jnci/djv306 |
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