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Gain of ALK Gene Copy Number May Predict Lack of Benefit from Anti-EGFR Treatment in Patients with Advanced Colorectal Cancer and RAS-RAF-PI3KCA Wild-Type Status
INTRODUCTION: Although cetuximab and panitumumab show an increased efficacy for patients with KRAS-NRAS-BRAF and PI3KCA wild-type metastatic colorectal cancer, primary resistance occurs in a relevant subset of molecularly enriched populations. PATIENTS AND METHODS: We evaluated the outcome of 68 pat...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972159/ https://www.ncbi.nlm.nih.gov/pubmed/24691006 http://dx.doi.org/10.1371/journal.pone.0092147 |
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author | Pietrantonio, Filippo Maggi, Claudia Di Bartolomeo, Maria Facciorusso, Maria Grazia Perrone, Federica Testi, Adele Iacovelli, Roberto Miceli, Rosalba Bossi, Ilaria Leone, Giorgia Milione, Massimo Pelosi, Giuseppe de Braud, Filippo |
author_facet | Pietrantonio, Filippo Maggi, Claudia Di Bartolomeo, Maria Facciorusso, Maria Grazia Perrone, Federica Testi, Adele Iacovelli, Roberto Miceli, Rosalba Bossi, Ilaria Leone, Giorgia Milione, Massimo Pelosi, Giuseppe de Braud, Filippo |
author_sort | Pietrantonio, Filippo |
collection | PubMed |
description | INTRODUCTION: Although cetuximab and panitumumab show an increased efficacy for patients with KRAS-NRAS-BRAF and PI3KCA wild-type metastatic colorectal cancer, primary resistance occurs in a relevant subset of molecularly enriched populations. PATIENTS AND METHODS: We evaluated the outcome of 68 patients with advanced colorectal cancer and RAS, BRAF and PI3KCA status according to ALK gene status (disomic vs. gain of ALK gene copy number – defined as mean of 3 to 5 fusion signals in ≥10% of cells). All consecutive patients received cetuximab and irinotecan or panitumumab alone for chemorefractory disease. RESULTS: No ALK translocations or amplifications were detected. ALK gene copy number gain was found in 25 (37%) tumors. Response rate was significantly higher in patients with disomic ALK as compared to those with gain of gene copy number (70% vs. 32%; p = 0.0048). Similarly, progression-free survival was significantly different when comparing the two groups (6.7 vs. 5.3 months; p = 0.045). A trend was observed also for overall survival (18.5 vs. 15.6 months; p = 0.885). CONCLUSION: Gain of ALK gene copy number might represent a negative prognostic factor in mCRC and may have a role in resistance to anti-EGFR therapy. |
format | Online Article Text |
id | pubmed-3972159 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39721592014-04-04 Gain of ALK Gene Copy Number May Predict Lack of Benefit from Anti-EGFR Treatment in Patients with Advanced Colorectal Cancer and RAS-RAF-PI3KCA Wild-Type Status Pietrantonio, Filippo Maggi, Claudia Di Bartolomeo, Maria Facciorusso, Maria Grazia Perrone, Federica Testi, Adele Iacovelli, Roberto Miceli, Rosalba Bossi, Ilaria Leone, Giorgia Milione, Massimo Pelosi, Giuseppe de Braud, Filippo PLoS One Research Article INTRODUCTION: Although cetuximab and panitumumab show an increased efficacy for patients with KRAS-NRAS-BRAF and PI3KCA wild-type metastatic colorectal cancer, primary resistance occurs in a relevant subset of molecularly enriched populations. PATIENTS AND METHODS: We evaluated the outcome of 68 patients with advanced colorectal cancer and RAS, BRAF and PI3KCA status according to ALK gene status (disomic vs. gain of ALK gene copy number – defined as mean of 3 to 5 fusion signals in ≥10% of cells). All consecutive patients received cetuximab and irinotecan or panitumumab alone for chemorefractory disease. RESULTS: No ALK translocations or amplifications were detected. ALK gene copy number gain was found in 25 (37%) tumors. Response rate was significantly higher in patients with disomic ALK as compared to those with gain of gene copy number (70% vs. 32%; p = 0.0048). Similarly, progression-free survival was significantly different when comparing the two groups (6.7 vs. 5.3 months; p = 0.045). A trend was observed also for overall survival (18.5 vs. 15.6 months; p = 0.885). CONCLUSION: Gain of ALK gene copy number might represent a negative prognostic factor in mCRC and may have a role in resistance to anti-EGFR therapy. Public Library of Science 2014-04-01 /pmc/articles/PMC3972159/ /pubmed/24691006 http://dx.doi.org/10.1371/journal.pone.0092147 Text en © 2014 Pietrantonio et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Pietrantonio, Filippo Maggi, Claudia Di Bartolomeo, Maria Facciorusso, Maria Grazia Perrone, Federica Testi, Adele Iacovelli, Roberto Miceli, Rosalba Bossi, Ilaria Leone, Giorgia Milione, Massimo Pelosi, Giuseppe de Braud, Filippo Gain of ALK Gene Copy Number May Predict Lack of Benefit from Anti-EGFR Treatment in Patients with Advanced Colorectal Cancer and RAS-RAF-PI3KCA Wild-Type Status |
title | Gain of ALK Gene Copy Number May Predict Lack of Benefit from Anti-EGFR Treatment in Patients with Advanced Colorectal Cancer and RAS-RAF-PI3KCA Wild-Type Status |
title_full | Gain of ALK Gene Copy Number May Predict Lack of Benefit from Anti-EGFR Treatment in Patients with Advanced Colorectal Cancer and RAS-RAF-PI3KCA Wild-Type Status |
title_fullStr | Gain of ALK Gene Copy Number May Predict Lack of Benefit from Anti-EGFR Treatment in Patients with Advanced Colorectal Cancer and RAS-RAF-PI3KCA Wild-Type Status |
title_full_unstemmed | Gain of ALK Gene Copy Number May Predict Lack of Benefit from Anti-EGFR Treatment in Patients with Advanced Colorectal Cancer and RAS-RAF-PI3KCA Wild-Type Status |
title_short | Gain of ALK Gene Copy Number May Predict Lack of Benefit from Anti-EGFR Treatment in Patients with Advanced Colorectal Cancer and RAS-RAF-PI3KCA Wild-Type Status |
title_sort | gain of alk gene copy number may predict lack of benefit from anti-egfr treatment in patients with advanced colorectal cancer and ras-raf-pi3kca wild-type status |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972159/ https://www.ncbi.nlm.nih.gov/pubmed/24691006 http://dx.doi.org/10.1371/journal.pone.0092147 |
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