Plasma HSP90α and liver cancer: a potential biomarker?

Liver cancer comprises multiple kind of primary liver cancers (cancers that rise from the liver) as well as secondary liver cancers (cancers that rise from other organs). Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and is also one of the most lethal cancer in the world (Waller et al., 2015). Other types of primary liver cancers include intrahepatic cholangiocarcinoma (CC) which represents about 10% of cases, and angiosarcoma, hemangiosarcoma and hepatoblastomawhich are rare. There are currently limited therapeutic options for patients with primary liver cancer and recurrence rates after surgery are elevated. Survival rates are also very low with an average 5 year-survival rate of 17.6% in the US and b6% worldwide. Indeed, most cases are being diagnosed at an advance stage: only 43% of cases at diagnosis are localized diseases (5 year-survival rate of 31.1%), 27% are regional (5 year-survival rate of 10.1%), 18% are distant (5 year-survival rate of 2.8%) and 12% are unstaged/unknown (5 year-survival rate of 6.4%) [data for US population, SEER website]. Thus, the development of sensitive biomarkers for diagnosis and response to therapy is highly needed. Because of the steady increase in incidence of liver cancer (over 2% per year), there has been a global push to expand our knowledge and understanding of primary liver cancers, especially HCC. Recently, large scale genomic studies have identified multiple mutations and delineated potential therapeutic targets (Ally et al., 2017; Schulze et al., 2015; Totoki et al., 2014). However, these findings have yet to be translated into the clinic. Until then, early detection of all primary liver cancers is critical. Several serological, molecular and pathological biomarkers have been used and/or proposed for liver cancer (Behne and Copur, 2012). For example, alpha-fetoprotein (AFP) has been a standard serological biomarker, but its lack of sensitivity and specificity are prompting the development of more potent biomarkers. HSP90α is a molecular chaperone involved inmultiple physiological and pathological signaling pathways. In multiple cancers, HSP90α is overexpressed (including in HCC) and can be secreted outside the tumor cells (Eustace et al., 2004; Lu et al., 2015) Although the extracellular role of HSP90a is still not fully understood, it is known to promote metastases (Eustace et al., 2004). In EBioMedicine, Fu and collaborators recently investigated whether levels of plasma HSP90α in liver cancer patients could improve diagnosis accuracy and be predictive of response to therapy (Fu et al., 2017). This report follows an earlier publication evaluating the role of