CTR1 may be required for successful platinum-based therapy in NSCLC

May 19 2014

By Laura Cowen, medwireNews Reporter

Tumours with undetectable levels of the copper transporter CTR1 have a significantly reduced response to platinum-based chemotherapy for non-small-cell lung cancer (NSCLC), study findings indicate.

This suggests that “CTR1 expression may be necessary for therapeutic efficacy of platinum drugs,” write Eric Kim (University of Rochester, New York, USA) and co-authors in Lung Cancer.

Kim and team previously showed that low tissue platinum concentration in NSCLC specimens was significantly associated with reduced tumour response, and other groups have demonstrated that low expression of CTR1, a transporter of platinum uptake, was associated with poor clinical outcome following platinum-based therapy.

The current study investigated the relationship between intratumoural platinum concentration and CTR1 expression in paraffin-embedded NSCLC tissue block samples from 30 patients who underwent neoadjuvant platinum-based chemotherapy prior to surgical resection and had previously measured tissue platinum levels.

CTR1 expression, determined by immunohistochemistry, was detected in all but two of the tumour samples, with 70% of specimens having scores of 2+ or 3+ on a scale of 0 to 3+. The researchers also tested normal adjacent lung tissue for 25 of the 30 samples but found no correlation in CTR1 expression between the two tissue types.

There was no significant difference in platinum concentration when compared across the four different immunohistochemistry score groups for CTR1 expression. However, tumours with undetectable CTR1 expression (score of 0) had a considerably lower platinum concentration compared with the other three groups combined, at 0.0011 versus 0.0033 absorbance units/mg of tissue, which was of borderline statistical significance.

Furthermore, patients with no expression of CTR1 had a response rate of 0% compared with a significantly greater 29% for those with any level of CTR1 expression.

Kim et al noted that both patients with undetectable CTR1 expression in their tumours were African American, and therefore conducted further analyses based on ethnicity.

They observed a significant difference in CTR1 expression score between Caucasians and African Americans as well as significantly reduced intratumoural platinum concentrations and tumour response. There was not, however, a corresponding difference between the two groups in the normal adjacent epithelial specimens.

The researchers conclude that their findings “warrant further investigation of CTR1 as a potential biomarker for platinum therapy in NSCLC.”

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