Researchers Look to Improve Late-Stage Liver Cancer Therapy

Scientists discovered a potential therapy for late-stage liver cancer based on earlier work showing that the androgen receptor (AR), the protein that makes testosterone functional, plays a major role in regulating this type of malignancy.   

Studies have found that AR has an unusual, dual role in liver cancer: it seems to stimulate cancer cells during initiation of the disease, but then it can suppress cancer in later stages and when metastasis occurs. The goal of the research team based at the University of Rochester’s Wilmot Cancer Institute was to focus on late-stage liver cancer—and investigate whether boosting AR expression would help to stop the disease from spreading by making cancer cells more sensitive to a newly approved chemotherapy called Sorafenib. In laboratory experiments in mice and human tissue, scientists working with Chawnshang Chang, Ph.D., identified a microRNA molecule (miR-367-3p) that correlates with AR to suppress liver cancer metastasis, they reported in an article published online by eBioMedicine.

The team not only identified miR-367-3p as a potential metastasis biomarker, but also the gene pathways that miR-367-3p targets to increase AR expression. After additional study, researchers believe that miR-367-3p, as an AR enhancer, could be tested in clinical trials in combination with other therapies to stabilize or treat late-stage or metastatic liver cancer.

Liver cancer (hepatocellular carcinoma) is relatively rare but the incidence has been rising in the U.S. and elsewhere. Five-year survival rates are low at 15 percent to 30 percent for localized disease and even lower for advanced liver cancer. A liver transplant can cure some patients, but not everyone qualifies depending on the stage of cancer and other health problems.

Corresponding co-authors on the paper are Chang and Xuijun Cai, M.D., Ph.D., along with their teams at the George Whipple Lab for Cancer Research at the UR and scientists at the Chawnshang Chang Liver Cancer Treatment Center at Zhejiang University in China. First author Junjie Xu, M.D., and a Ph.D. candidate, wrote the manuscript and carried out major parts of the project.

Chang’s lab has been studying the androgen receptor in the context of several cancers for many years. In 2010 one of his studies analyzed why men get liver cancer more often than women—even when people of both genders have been exposed to hepatitis infection, a major risk factor. The study showed a direct link between AR and the hepatitis B virus.

Additional co-authors include Hui Lin, Yin Sun, Jiang Chen, and Liang Shi.  Funding was provided by the National Institutes of Health, the George Whipple Professorship Endowment, Taiwan Department of Health Clinical Trial Research Center, Natural Science Foundation of Zhejiang Province, National Natural Science Foundation of China, and scientific-technology cooperative projects.

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