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

Research output: Contribution to journalJournal articlepeer-review

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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; Hgdall, Estrid Vilma Solyom; Poulsen, Tim Svenstrup; Linnemann, Dorte; Nygaard, Sune Boris; Stenvang, Jan; Christensen, Ib Jarle; Jensen, Benny Vittrup; Pfeiffer, Per; Brunner, Nils; Yilmaz, Mette; Viuff, Birgitte Martine; Nielsen, Dorte Lisbet.

In: International Journal of Molecular Sciences, Vol. 21, No. 14, 5027, 2020.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Palshof, JA, Cederbye, CN, Hgdall, EVS, Poulsen, TS, Linnemann, D, Nygaard, SB, Stenvang, J, Christensen, IJ, Jensen, BV, Pfeiffer, P, Brunner, N, Yilmaz, M, Viuff, BM & Nielsen, DL 2020, 'ABCG2 Protein Levels and Association to Response to First-Line Irinotecan-Based Therapy for Patients with Metastatic Colorectal Cancer', International Journal of Molecular Sciences, vol. 21, no. 14, 5027. https://doi.org/10.3390/ijms21145027

APA

Palshof, J. A., Cederbye, C. N., Hgdall, E. V. S., Poulsen, T. S., Linnemann, D., Nygaard, S. B., Stenvang, J., Christensen, I. J., Jensen, B. V., Pfeiffer, P., Brunner, N., Yilmaz, M., Viuff, B. M., & Nielsen, D. L. (2020). ABCG2 Protein Levels and Association to Response to First-Line Irinotecan-Based Therapy for Patients with Metastatic Colorectal Cancer. International Journal of Molecular Sciences, 21(14), [5027]. https://doi.org/10.3390/ijms21145027

Vancouver

Palshof JA, Cederbye CN, Hgdall EVS, Poulsen TS, Linnemann D, Nygaard SB et al. ABCG2 Protein Levels and Association to Response to First-Line Irinotecan-Based Therapy for Patients with Metastatic Colorectal Cancer. International Journal of Molecular Sciences. 2020;21(14). 5027. https://doi.org/10.3390/ijms21145027

Author

Palshof, Jesper Andreas ; Cederbye, Camilla Natasha ; Hgdall, Estrid Vilma Solyom ; Poulsen, Tim Svenstrup ; Linnemann, Dorte ; Nygaard, Sune Boris ; Stenvang, Jan ; Christensen, Ib Jarle ; Jensen, Benny Vittrup ; Pfeiffer, Per ; Brunner, 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. In: International Journal of Molecular Sciences. 2020 ; Vol. 21, No. 14.

Bibtex

@article{cbec7877a52446bbbec9672713803a48,
title = "ABCG2 Protein Levels and Association to Response to First-Line Irinotecan-Based Therapy for Patients with Metastatic Colorectal Cancer",
abstract = "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.",
keywords = "biomarker, colorectal cancer, ABCG2 protein, BCRP, irinotecan, RESISTANCE PROTEIN, EXPRESSION, CHEMOTHERAPY, GUIDELINES",
author = "Palshof, {Jesper Andreas} and Cederbye, {Camilla Natasha} and Hgdall, {Estrid Vilma Solyom} and Poulsen, {Tim Svenstrup} and Dorte Linnemann and Nygaard, {Sune Boris} and Jan Stenvang and Christensen, {Ib Jarle} and Jensen, {Benny Vittrup} and Per Pfeiffer and Nils Brunner and Mette Yilmaz and Viuff, {Birgitte Martine} and Nielsen, {Dorte Lisbet}",
year = "2020",
doi = "10.3390/ijms21145027",
language = "English",
volume = "21",
journal = "International Journal of Molecular Sciences (Online)",
issn = "1661-6596",
publisher = "MDPI AG",
number = "14",

}

RIS

TY - JOUR

T1 - ABCG2 Protein Levels and Association to Response to First-Line Irinotecan-Based Therapy for Patients with Metastatic Colorectal Cancer

AU - Palshof, Jesper Andreas

AU - Cederbye, Camilla Natasha

AU - Hgdall, Estrid Vilma Solyom

AU - Poulsen, Tim Svenstrup

AU - Linnemann, Dorte

AU - Nygaard, Sune Boris

AU - Stenvang, Jan

AU - Christensen, Ib Jarle

AU - Jensen, Benny Vittrup

AU - Pfeiffer, Per

AU - Brunner, Nils

AU - Yilmaz, Mette

AU - Viuff, Birgitte Martine

AU - Nielsen, Dorte Lisbet

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - biomarker

KW - colorectal cancer

KW - ABCG2 protein

KW - BCRP

KW - irinotecan

KW - RESISTANCE PROTEIN

KW - EXPRESSION

KW - CHEMOTHERAPY

KW - GUIDELINES

U2 - 10.3390/ijms21145027

DO - 10.3390/ijms21145027

M3 - Journal article

C2 - 32708825

VL - 21

JO - International Journal of Molecular Sciences (Online)

JF - International Journal of Molecular Sciences (Online)

SN - 1661-6596

IS - 14

M1 - 5027

ER -

ID: 248895901