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ABC-Transporter Expression Does Not Correlate with Response to Irinotecan in Patients with Metastatic Colorectal

K Trumpi1, B L Emmink1, A M Prins1

  • 11. Department of Surgery, University Medical Centre Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands.

Journal of Cancer
|October 31, 2015
PubMed
Abstract

Insights

ATP-binding cassette (ABC)-transporter expression, specifically ABCB1 and ABCG2, does not predict irinotecan response in metastatic colorectal cancer (CRC) patients. This finding is crucial for understanding drug resistance in CRC treatment.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Active efflux by ATP-binding cassette (ABC)-transporters (ABCB1, ABCG2) is a known irinotecan resistance mechanism in vitro and in pre-clinical models.
  • The clinical relevance of this mechanism in colorectal cancer (CRC) patients remains undetermined.

Purpose of the Study:

  • To investigate the association between ABCB1 and ABCG2 transporter expression and patient response to irinotecan in metastatic CRC.
  • To determine if ABC-transporter expression in primary tumors can predict treatment outcomes.

Main Methods:

  • Analysis of ABCB1 and ABCG2 expression using immunohistochemistry on tissue microarrays from 566 metastatic CRC patients (CAIRO study).
  • Kaplan-Meier and Cox regression analyses to correlate transporter expression with irinotecan response.
  • Assessment of ABCB1/ABCG2 expression concordance between primary CRC and paired metastases using gene expression profiles.

Main Results:

  • No significant difference in irinotecan response (progression-free survival) based on positive or negative ABCB1 or ABCG2 expression.
  • Multivariate analysis confirmed that neither ABCB1 nor ABCG2 independently predicted progression-free survival.
  • Mediocre to poor concordance was observed between ABC-transporter expression in primary tumors and their corresponding metastases.

Conclusions:

  • ABC-transporter expression in primary tumors of metastatic CRC patients does not serve as a predictor of response to irinotecan.
  • These findings suggest that other mechanisms may be more critical in determining irinotecan efficacy in this patient population.
Keywords:
ABC-transportersABCB1ABCG2CAIROIrinotecanchemotherapymetastatic colorectal cancer

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