Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings.
Vol 23, No 16S (June 1 Supplement), 2005: 9603
© 2005 American Society of Clinical Oncology

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Abstract

Copper (Cu) transporter ATP7B mRNA levels as a prognostic factor in advanced colorectal cancer patients treated with 5-fluorouracil (5FU) plus oxaliplatin combination

Inst Català d’Oncologia, Hosp Univ, Badalona, Spain; Univ of Southern CA, Los Angeles, CA; Hosp Germans Trias i Pujol, Badalona, Spain

9603

Background: Previous studies in yeast and human cell lines have demonstrated that Cu transporter ATP7B can mediate resistance to platinum drugs such as Cisplatin, Carboplatin and Oxaliplatin. ATP7B is a P-Type ATPase (mutated in Wilson’s disease) located in the trans-Golgi network that pumps Cu into secretory compartments. Recent studies have demonstrated a correlation between ATP7B protein and/or mRNA levels and outcome in ovarian cancer patients who were treated with a Cisplatin-based chemotherapy. The aim of this study was to evaluate ATP7B expression in tumors from colorectal cancer patients treated with Oxaliplatin plus 5FU (TTD schedule) and its correlation with the outcome. Methods: Total RNA was obtained from paraffin embedded tissues and real time quantitative RTPCR was used to assess the relative expression of ATP7B. Beta-Actin was used as an endogenous control and placenta RNA as a reference. Results: We analyzed 24 metastatic colorectal cancer patients treated with Oxaliplatin plus 5FU. 62.15% were males; 66.7% colon, 33.3% rectum; median ATP7B mRNA expression levels was 0.27 and was used as a cutoff to separate the patients. 61.5% of patients with mRNA levels lower than the cutoff responded to chemotherapy whereas only 27.3% of those who had high levels of ATP7B responded. Median TTP was 7.45 months for the low expression group and 3.1 months for patients in the high expression group (P=0.04 log-rank test). Conclusions: Our data show the importance of ATP7B gene expression in the outcome of colorectal cancer patients treated with Oxaliplatin. Low levels of expression correlated with better response and TTP. These results can open new pharmacogenetic approaches to individualize chemotherapy in colorectal cancer patients to be treated with or without Oxaliplatin.

No significant financial relationships to disclose.

Abstract presentation from the 2005 ASCO Annual Meeting