Liver Cancer and Fibrosis-Cirrhosis

Hepatocellular carcinoma (HCC)—cancer of the liver parenchyma and the most common form of liver cancer—is the fifth most prevalent form of cancer worldwide and the third leading cause of cancer death, killing approximately 700,000 each year. In the US, HCC is one of the few forms of cancer whose incidence is increasing and is the fastest growing cause of cancer mortality. Cholangiocarcinoma (CCA)—cancer of the biliary tree and bile duct—is the second most common form of liver cancer. Overall survival for both HCC and CCA is limited, as the vast majority of patients currently present with symptomatic, late-stage disease ineligible for potentially curative treatment. Early detection of HCC and CCA remains a serious unmet clinical need. Effective non-invasive monitoring of liver fibrosis also remains a challenge, with core biopsy still regarded as the “gold standard”.

Populations at risk for liver fibrosis-cirrhosis and HCC largely fall into two categories. Viral hepatitis—chronic hepatitis B and C infections—historically has been the most important predisposing condition. Hepatitis B, especially in Asian populations, is a significant cause of progressive fibrosis-cirrhosis and HCC, with half of all HCC deaths worldwide occurring in China. In the US hepatitis C is an even more prevalent threat. However, skyrocketing obesity and fatty liver disease and the non-viral hepatitis (NASH; non-alcoholic steatohepatitis) they cause are making liver cancer an increasingly Western health threat. The scope of this challenge for early detection is made clear by estimates that up to 15 million people in the US have NASH and one-third of the total US population has fatty liver disease.

Glycotest Technology

Glycotest blood tests are being developed to provide information on the likelihood of serious liver disease like cancer or fibrosis-cirrhosis by employing technology designed to measure two kinds of disease signals:

• The amount of the monosaccharide fucose that appears abnormally on certain serum glycoproteins—to indicate likelihood of disease.

• The pattern of glycoproteins that is abnormally fucosylated—to monitor specific diseases like HCC, CCA or fibrosis-cirrhosis.

The levels of the fucosylated serum glycoproteins that Glycotest targets are low in healthy individuals. However, in people with liver cancers or fibrosis-cirrhosis, specific fucose-containing glycoproteins, which we have identified, appear in the blood at abnormally high levels. Using proprietary assay technology based on engineered recombinant lectins, fucosylated proteins are measured in the sera of patients at risk due to underlying chronic liver conditions such as hepatitis. These measurements may then alert healthcare professionals to provide additional care to patients who are otherwise healthy and asymptomatic but have worsening liver disease.

Using common core biomarkers for multiple liver diseases, Glycotest’s technology can be deployed in panels or single biomarker tests that may exhibit performance characteristics superior to currently available tests. For example, AFP (alpha-fetoprotein) is a commonly used biomarker for HCC that unfortunately is secreted by as few as 50% of tumors. In other cases, like CCA, there are no currently accepted blood tests. And for liver fibrosis-cirrhosis, the challenge for existing tests has been the effective identification of intermediate stage disease. Glycotest’s technology has the potential to address these unmet diagnostic needs.