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Copper transporter CTR1 expression and tissue platinum concentration in non-small cell lung cancer. Lung Cancer 2014 Jul;85(1):88-93 PMID: 24792335 PMCID: PMC4090351

Pubmed ID

24792335

DOI

10.1016/j.lungcan.2014.04.005

Abstract

BACKGROUND: Platinum resistance is a major limitation in the treatment of advanced non-small cell lung cancer (NSCLC). We previously demonstrated that low tissue platinum concentration in NSCLC specimens was significantly associated with reduced tumor response. Furthermore, low expression of the copper transporter CTR1, a transporter of platinum uptake was associated with poor clinical outcome following platinum-based therapy in NSCLC patients. We investigated the relationship between tissue platinum concentrations and CTR1 expression in NSCLC specimens.

METHODS: We identified paraffin-embedded NSCLC tissue blocks of known tissue platinum concentrations from 30 patients who underwent neoadjuvant platinum-based chemotherapy at MD Anderson Cancer Center. Expression of CTR1 in tumors and normal adjacent lung specimens was determined by immunohistochemistry with adequate controls.

RESULTS: Tissue platinum concentration significantly correlated with tumor response in 30 patients who received neoadjuvant platinum-based chemotherapy (P<0.001). CTR1 was differentially expressed in NSCLC tumors. A subset of patients with undetectable CTR1 expression in their tumors had reduced platinum concentrations (P=0.058) and tumor response (P=0.016) compared to those with any level of CTR1 expression. We also observed that African Americans had significantly reduced CTR1 expression scores (P=0.001), tissue platinum concentrations (P=0.009) and tumor shrinkage (P=0.016) compared to Caucasians.

CONCLUSIONS: To our best knowledge this is the first study investigating the function of CTR1 in clinical specimens. CTR1 expression may be necessary for therapeutic efficacy of platinum drugs, consistent with previous preclinical studies. A prospective clinical trial is necessary to develop CTR1 into a potential biomarker for platinum drugs.

Author List

Kim ES, Tang X, Peterson DR, Kilari D, Chow CW, Fujimoto J, Kalhor N, Swisher SG, Stewart DJ, Wistuba II, Siddik ZH

Author

Deepak Kilari MD Assistant Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-84901624214   27 Citations

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Adult
African Americans
Aged
Carboplatin
Carcinoma, Non-Small-Cell Lung
Cation Transport Proteins
Chemotherapy, Adjuvant
Cisplatin
Drug Resistance, Neoplasm
European Continental Ancestry Group
Female
Humans
Lung
Lung Neoplasms
Male
Middle Aged
Neoadjuvant Therapy
Tumor Burden
jenkins-FCD Prod-310 bff9d975ec7f2d302586822146c2801dd4449aad