Published online Jan 7, 2016. doi: 10.3748/wjg.v22.i1.221
Peer-review started: May 12, 2015
First decision: August 25, 2015
Revised: October 18, 2015
Accepted: November 13, 2015
Article in press: November 13, 2015
Published online: January 7, 2016
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC. Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells. Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis. Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans. Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography (PET) using radioactive copper as a tracer. It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer, suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake. In addition to copper modulation therapy with copper chelators, short-interference RNA specific for human copper transporter 1 (hCtr1) may be used to suppress growth of HCC by blocking increased copper uptake mediated by hCtr1. Furthermore, altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides. Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC.
Core tip: Copper is required for cell proliferation and tumor angiogenesis. This article provided an up-to-date review of copper metabolism as a novel theranostic biomarker in hepatocellular carcinoma. Altered copper metabolism is not only a novel biomarker for molecular imaging of extrahepatic metastasis of hepatocellular carcinoma using radioactive copper, but is also a promising target for copper modulation and radionuclide therapy of hepatocellular carcinoma.