ABCG2 Protein Levels and Association to Response to First-Line Irinotecan-Based Therapy for Patients with Metastatic Colorectal Cancer
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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 journal › Journal article › peer-review
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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