Abstract
Purpose of Review: Intrahepatic cholangiocarcinoma (ICC) is a treatment-refractory disease with a dismal outcome. Limited success in the clinical management and a persistent increase in the incidence world-wide have made ICC one of the most lethal and fastest growing malignancies. However, recent advancements in genome-wide technologies combined with the application of integrative multidimensional analytical approaches have begun to provide both detailed insight into the underlying biological traits of ICC and identified new therapeutic opportunities. Recent Findings: In comparison with other cancers, genomic studies of ICC have been limited. We and others have recently procured large cohorts of ICC patients intended for genome-wide analyses. In our study, samples from ICC patients were obtained from three cancer centers and subjected to integrated genetic and genomic analyses. We provided new insights into both pathogenesis and optimal treatment options demonstrating the presence of unique subclasses of patients, based partly on KRAS mutations and increased levels of receptor tyrosine kinase signaling. The group of patients with the worst prognosis was characterized by transcriptional enrichment of genes regulating inflammation and proteasome activities, suggesting a combination of tyrosine kinase inhibitors and anti-inflammatory drugs as a new therapeutic option for these patients. Summary: We have critically examined the progress in genome-wide studies of ICC including genetic profiling, transcriptomics, and epigenomics. Current limitations in applying these technologies to archival samples and the insufficient access to fresh-frozen material are partly the cause of the delayed implementation of the omics-based investigations of ICC compared to other hepatobiliary diseases. Thus, selected candidate single-gene studies will also be discussed.
| Original language | English |
|---|---|
| Journal | Current Opinion in Gastroenterology |
| Volume | 28 |
| Issue number | 3 |
| Pages (from-to) | 266-72 |
| Number of pages | 7 |
| ISSN | 0267-1379 |
| DOIs | |
| Publication status | Published - May 2012 |
| Externally published | Yes |
Keywords
- Anti-Inflammatory Agents
- Cholangiocarcinoma
- DNA Mutational Analysis
- Drug Therapy, Combination
- Female
- Gene Expression Profiling
- Genes, ras
- Genome-Wide Association Study
- Humans
- Liver Neoplasms
- Male
- Mutation
- Patient Selection
- Prognosis
- Pyrazoles
- Pyrimidines
- Risk Factors
