Hershey, Pa. -- A more personalized treatment for people with a type of metastatic liver cancer -- hepatocellular carcinoma -- may be possible by targeting the protein c-Met, according to Penn State College of Medicine researchers. Hepatocellular carcinoma (HCC) is the No. 3 cause of cancer deaths in the world.
Hanning You, postdoctoral fellow, and C. Bart Rountree, assistant professor of pediatrics and pharmacology, targeted c-Met, a known receptor for hepatocyte growth factor, the substance that appears to drive liver cancer metastasis. In a pre-clinical translational study, they show that c-Met is overexpressed in metastatic liver cancer cells and is associated with a poor prognosis.
"In addition to finding that c-Met is a significant biomarker for liver cancer, we conducted an analysis of six published manuscripts and 1,051 patients," said You. "Through this analysis we demonstrated and confirmed that c-Met activation is strongly associated with poor prognosis and aggressive features in patients with liver cancer tumors."
Currently, physicians treat hepatocellular carcinoma with a "one size fits all" approach, so targeting c-Met may be an effective therapy for some patients.
"The five-year-survival of HCC is only 2 percent when diagnosed after metastasis," said Rountree. "Sorafenib, the most recently approved mediation for advanced HCC, benefits patients with an extra two months survival."
By targeting c-Met, researchers suppressed tumor growth and proliferation in a mouse model. They believe that molecular profiling will allow better treatment for the 45 percent of HCC patients who have c-Met positive tumors.
The research team is now looking to apply their findings to HCC in humans. The lab has applied to the National Cancer Institute to join a phase I trial using a c-Met inhibitor for advanced HCC.
"We are also working to build a second trial where we will establish a molecular profile of HCC patients before we start treatment, and then only give the c-Met inhibitor to the patients with a c-Met positive tumor, in effect personalizing their therapy," Rountree said.
Funding was provided by Children’s Miracle Network, National Institutes of Health, American Cancer Society and Clinical and Translational Science Institute.