Researchers one step closer to treatment of rare cancer
Bile duct cancer is a rare tumour type, which is associated with a poor prognosis. Now, Danish and international researchers have performed an integrated molecular analysis of biliary tumours that not only gives scientists new information about this malignancy but also may lead to new treatments in the future.
Cholangiocarcinoma, also known as bile duct cancer, is a rare cancer type that originates in the body’s biliary tree, either inside or outside the liver. The prognosis for bile duct cancer is extremely poor; both because the disease is often diagnosed at an advanced stage and does not respond well to conventional chemotherapies. Bile ducts cancer is caused by both environmental and genetic factors, and due to the diverse origin, researchers lack an understanding of the mechanisms behind the disease. A group of researchers from The Cancer Genome Atlas (TCGA) Research Network have just published a new study in the journal Cell Reports, where they investigate the molecular mechanisms behind this rare cancer type.
"We are dealing with a type of cancer where patients' chances of survival have not improved since the 1980s. The incidence of bile duct cancer is on the rise despite better diagnostic methods and generally far better therapies. It is just not good enough! To improve our understanding of why bile duct cancer occurs in these patients, it is necessary to form a complete map of their genome, and specifically the causal changes," says Associate professor and co-author Jesper B Andersen, Biotech Research & Innovation Centre, University of Copenhagen.
Different treatment for different patients
In order to understand the mechanisms of bile duct cancer, researchers grouped patients according to their gene expression, DNA methylation and copies of the genome. Using Cluster-of-Cluster (COCA) analysis, researchers identified 4 different patient groups. One group is characterized by changes in the gene IDH which is associated with reduced expression of genes, whose role is to change the architecture of DNA, and further increased levels of genes involved in mitochondrial metabolism (OXPHOS). This marks a potential unique mechanism for the development of IDH-related bile duct cancer. Other unique patient groups, in which the team behind the study identified are either related to patients with multiple copies of the gene cyclin D1 or FGFR2 fusions.
"For the first time, we have successfully shown that patients with bile duct cancer can be stratified into distinct groups who are molecularly different, and therefore should be treated differently. Comparison of bile duct cancer at the genomic level with other forms of liver cancers (read: hepatocellular carcinoma) supports previous studies in experimental models, and shows that bile duct cancer, which arises in the bile ducts, is part of a continuous spectrum of liver cancer. Therefore, it is now clear that molecular technology should be considered as a supplement to ensure correct classification of some patients with liver cancer," Jesper B Andersen explains.
Since the number of patients in this study is relatively small, further research is needed. Therefore, the next step for Jesper B Andersen and his research team at BRIC is to further investigate the new grouping of patients with bile duct cancer and their biological characteristics in a larger study.
‘Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles’. Cell Reports (2017). doi: 10.1016/j.celrep.2017.02.033