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.
<h4>Introduction</h4>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.<h4>Patients and methods</h4&...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0092147&type=printable |
| _version_ | 1826799222968549376 |
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| author | Filippo Pietrantonio Claudia Maggi Maria Di Bartolomeo Maria Grazia Facciorusso Federica Perrone Adele Testi Roberto Iacovelli Rosalba Miceli Ilaria Bossi Giorgia Leone Massimo Milione Giuseppe Pelosi Filippo de Braud |
| author_facet | Filippo Pietrantonio Claudia Maggi Maria Di Bartolomeo Maria Grazia Facciorusso Federica Perrone Adele Testi Roberto Iacovelli Rosalba Miceli Ilaria Bossi Giorgia Leone Massimo Milione Giuseppe Pelosi Filippo de Braud |
| author_sort | Filippo Pietrantonio |
| collection | DOAJ |
| description | <h4>Introduction</h4>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.<h4>Patients and methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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. |
| first_indexed | 2024-12-10T16:32:58Z |
| format | Article |
| id | doaj.art-98a5cdfd99324a1685843733e9772dec |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2025-03-17T00:31:40Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-98a5cdfd99324a1685843733e9772dec2025-02-21T05:35:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9214710.1371/journal.pone.0092147Gain 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.Filippo PietrantonioClaudia MaggiMaria Di BartolomeoMaria Grazia FacciorussoFederica PerroneAdele TestiRoberto IacovelliRosalba MiceliIlaria BossiGiorgia LeoneMassimo MilioneGiuseppe PelosiFilippo de Braud<h4>Introduction</h4>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.<h4>Patients and methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0092147&type=printable |
| spellingShingle | Filippo Pietrantonio Claudia Maggi Maria Di Bartolomeo Maria Grazia Facciorusso Federica Perrone Adele Testi Roberto Iacovelli Rosalba Miceli Ilaria Bossi Giorgia Leone Massimo Milione Giuseppe Pelosi Filippo de Braud 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. PLoS ONE |
| 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 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0092147&type=printable |
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