Abcg2 protein levels and association to response to first-line irinotecan-based therapy for patients with metastatic colorectal cancer

Jesper Andreas Palshof, Camilla Natasha Cederbye, Estrid Vilma Solyom Høgdall, Tim Svenstrup Poulsen, Dorte Linnemann, Sune Boris Nygaard, Jan Stenvang, Ib Jarle Christensen, Benny Vittrup Jensen, Per Pfeiffer, Nils Brünner*, Mette Yilmaz, Birgitte Martine Viuff, Dorte Lisbet Nielsen

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Abstrakt

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.

OriginalsprogEngelsk
Artikelnummer5027
TidsskriftInternational Journal of Molecular Sciences
Vol/bind21
Udgave nummer14
Antal sider13
ISSN1661-6596
DOI
StatusUdgivet - jul. 2020

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  • Citationsformater

    Palshof, J. A., Cederbye, C. N., Høgdall, E. V. S., Poulsen, T. S., Linnemann, D., Nygaard, S. B., Stenvang, J., Christensen, I. J., Jensen, B. V., Pfeiffer, P., Brünner, 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