Gallbladder and Bile Duct Cancer

2008 News Archive

Genetic Analysis of Gallbladder Cancer Reveals Novel Biomarkers

The Hopkins' biliary cancer group hopes to utilize global gene expression profiling to identify new prognostic markers and therapeutic targets within gallbladder and bile duct cancers. Our goal is to use genetics to identify factors which make only the cancer cells grow, and which can therefore be specifically blocked via nontoxic but highly effective therapies.

In the May 1st , 2008 issue of Clinical Cancer Research, Hector Alvarez from our group has published the first study of gallbladder cancer using serial analysis of gene expression (SAGE). This method, first developed at Johns Hopkins, allows for an unbiased and quantitative assessment of mRNA expression from different tissue samples. This methodology facilitates the discovery of cancer biomarkers, imaging targets, and therapeutic avenues. For example, in 2001, our group used SAGE to identify mesothelin and prostate stem cell antigen as biomarkers and therapeutic targets for pancreatic cancer. Parenthetically, both of these proteins are also expressed in biliary cancer, allowing patients with biliary tract cancer to benefit from these discoveries.

Alvarez et al. performed serial analysis gene expression (SAGE) on three stage-matched gallbladder cancers (representing Hispanic/Latino, Native American, and Caucasian ethnicities, respectively) and one histologically normal gallbladder. In this study, Alvarez et al. determined that connective tissue growth factor (CTGF) was overexpressed in gallbladder cancer compared to normal gallbladder, and was associated with a relatively favorable prognosis. While the latter is an important piece of information, the true importance of this study is that the data generated from this exhaustive genetic analysis is publicly available online (http://cgap.nci.nih.gov) , and should allow for further analysis of genetic pathways which are altered in gallbladder cancer. This should allow for our group and others to identify pathways which can be targeted for therapy. For example, preliminary analysis of the gallbladder cancer SAGE libraries demonstrated upregulation of several genes in the mTOR pathway, suggesting that this may be a pathway which can be targeted. We look forward to using this incredible online dataset to further study this biliary tract cancer, and find novel, nontoxic avenues of treatment.

Reference:
Clinical Cancer Research 2008;14: 2631-8.

~ May 2008