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ABCG2 Protein Levels and Association to Response to First-Line Irinotecan-Based Therapy for Patients with Metastatic Colorectal Cancer

In this study we investigated the use of cancer cell protein expression of ABCG2 to predict efficacy of systemic first-line irinotecan containing therapy in patients with metastatic colorectal cancer (mCRC). From a Danish national cohort, we identified 119 mCRC patients treated with irinotecan conta...

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Autores principales: Palshof, Jesper Andreas, Cederbye, Camilla Natasha, Høgdall, Estrid Vilma Solyom, Poulsen, Tim Svenstrup, Linnemann, Dorte, Nygaard, Sune Boris, Stenvang, Jan, Christensen, Ib Jarle, Jensen, Benny Vittrup, Pfeiffer, Per, Brünner, Nils, Yilmaz, Mette, Viuff, Birgitte Martine, Nielsen, Dorte Lisbet
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404184/
https://www.ncbi.nlm.nih.gov/pubmed/32708825
http://dx.doi.org/10.3390/ijms21145027
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author Palshof, Jesper Andreas
Cederbye, Camilla Natasha
Høgdall, Estrid Vilma Solyom
Poulsen, Tim Svenstrup
Linnemann, Dorte
Nygaard, Sune Boris
Stenvang, Jan
Christensen, Ib Jarle
Jensen, Benny Vittrup
Pfeiffer, Per
Brünner, Nils
Yilmaz, Mette
Viuff, Birgitte Martine
Nielsen, Dorte Lisbet
author_facet Palshof, Jesper Andreas
Cederbye, Camilla Natasha
Høgdall, Estrid Vilma Solyom
Poulsen, Tim Svenstrup
Linnemann, Dorte
Nygaard, Sune Boris
Stenvang, Jan
Christensen, Ib Jarle
Jensen, Benny Vittrup
Pfeiffer, Per
Brünner, Nils
Yilmaz, Mette
Viuff, Birgitte Martine
Nielsen, Dorte Lisbet
author_sort Palshof, Jesper Andreas
collection PubMed
description In this study we investigated the use of cancer cell protein expression of ABCG2 to predict efficacy of systemic first-line irinotecan containing therapy in patients with metastatic colorectal cancer (mCRC). From a Danish national cohort, we identified 119 mCRC patients treated with irinotecan containing therapy in first-line setting. Among these, 108 were eligible for analyses. Immunohistochemistry (IHC) analyses were performed on the primary tumor tissue in order to classify samples as high or low presence of ABCG2 protein. Data were then associated with patient outcome (objective response (OR), progression free survival (PFS) and overall survival (OS)). ABCG2 protein expression in the basolateral membrane was high (score 3+) in 33% of the patients. Exploratory analyses revealed a significant interaction between ABCG2 score, adjuvant treatment and OR (p = 0.041) in the 101 patients with evaluable disease. Patients with low ABCG2 (score 0–2) and no prior adjuvant therapy had a significantly higher odds ratio of 5.6 (Confidence Interval (CI) 1.68–18.7; p = 0.005) for obtaining OR. In contrast, no significant associations between ABCG2 expression and PFS or OS were found. These results suggest that measurement of the ABCG2 drug efflux pump might be used to select patients with mCRC for irinotecan treatment. However, additional studies are warranted before conclusions regarding a clinical use can be made. Moreover, patients with high ABCG2 immunoreactivity could be candidates for specific ABCG2 inhibition treatment in combination with irinotecan.
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spelling pubmed-74041842020-08-11 ABCG2 Protein Levels and Association to Response to First-Line Irinotecan-Based Therapy for Patients with Metastatic Colorectal Cancer Palshof, Jesper Andreas Cederbye, Camilla Natasha Høgdall, Estrid Vilma Solyom Poulsen, Tim Svenstrup Linnemann, Dorte Nygaard, Sune Boris Stenvang, Jan Christensen, Ib Jarle Jensen, Benny Vittrup Pfeiffer, Per Brünner, Nils Yilmaz, Mette Viuff, Birgitte Martine Nielsen, Dorte Lisbet Int J Mol Sci Article In this study we investigated the use of cancer cell protein expression of ABCG2 to predict efficacy of systemic first-line irinotecan containing therapy in patients with metastatic colorectal cancer (mCRC). From a Danish national cohort, we identified 119 mCRC patients treated with irinotecan containing therapy in first-line setting. Among these, 108 were eligible for analyses. Immunohistochemistry (IHC) analyses were performed on the primary tumor tissue in order to classify samples as high or low presence of ABCG2 protein. Data were then associated with patient outcome (objective response (OR), progression free survival (PFS) and overall survival (OS)). ABCG2 protein expression in the basolateral membrane was high (score 3+) in 33% of the patients. Exploratory analyses revealed a significant interaction between ABCG2 score, adjuvant treatment and OR (p = 0.041) in the 101 patients with evaluable disease. Patients with low ABCG2 (score 0–2) and no prior adjuvant therapy had a significantly higher odds ratio of 5.6 (Confidence Interval (CI) 1.68–18.7; p = 0.005) for obtaining OR. In contrast, no significant associations between ABCG2 expression and PFS or OS were found. These results suggest that measurement of the ABCG2 drug efflux pump might be used to select patients with mCRC for irinotecan treatment. However, additional studies are warranted before conclusions regarding a clinical use can be made. Moreover, patients with high ABCG2 immunoreactivity could be candidates for specific ABCG2 inhibition treatment in combination with irinotecan. MDPI 2020-07-16 /pmc/articles/PMC7404184/ /pubmed/32708825 http://dx.doi.org/10.3390/ijms21145027 Text en © 2020 by the authors. 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/).
spellingShingle Article
Palshof, Jesper Andreas
Cederbye, Camilla Natasha
Høgdall, Estrid Vilma Solyom
Poulsen, Tim Svenstrup
Linnemann, Dorte
Nygaard, Sune Boris
Stenvang, Jan
Christensen, Ib Jarle
Jensen, Benny Vittrup
Pfeiffer, Per
Brünner, Nils
Yilmaz, Mette
Viuff, Birgitte Martine
Nielsen, Dorte Lisbet
ABCG2 Protein Levels and Association to Response to First-Line Irinotecan-Based Therapy for Patients with Metastatic Colorectal Cancer
title ABCG2 Protein Levels and Association to Response to First-Line Irinotecan-Based Therapy for Patients with Metastatic Colorectal Cancer
title_full ABCG2 Protein Levels and Association to Response to First-Line Irinotecan-Based Therapy for Patients with Metastatic Colorectal Cancer
title_fullStr ABCG2 Protein Levels and Association to Response to First-Line Irinotecan-Based Therapy for Patients with Metastatic Colorectal Cancer
title_full_unstemmed ABCG2 Protein Levels and Association to Response to First-Line Irinotecan-Based Therapy for Patients with Metastatic Colorectal Cancer
title_short ABCG2 Protein Levels and Association to Response to First-Line Irinotecan-Based Therapy for Patients with Metastatic Colorectal Cancer
title_sort abcg2 protein levels and association to response to first-line irinotecan-based therapy for patients with metastatic colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404184/
https://www.ncbi.nlm.nih.gov/pubmed/32708825
http://dx.doi.org/10.3390/ijms21145027
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