Genomic Decoding of Intrahepatic Cholangiocarcinoma Reveals Therapeutic Opportunities  Jesper B. Andersen, Snorri S. Thorgeirsson  Gastroenterology  Volume 144, Issue 4, Pages 687-690 (April 2013) DOI: 10.1053/j.gastro.2013.02.018 Copyright © 2013 AGA Institute Terms and Conditions

Figure 1 Classification and characterization of intrahepatic cholangiocarcinoma. An encouraging similarity in the prognostic classification and patient subgroup characterization is observed between the studies of Andersen et al7 and Sia et al,11 suggestive of several possible directions for future molecular targeted therapies in ICC. The “Class-specific approach” refers to the -omics–driven classification of patients versus the “Stratified strategy” where a patient is treated based on, for example, a genetic variant, regardless of the otherwise genomic classification. Patients with good outcomes (green classification, I 1–3 or subgroup I–II) are represented by a deregulated immune response suggesting a potential therapeutic application for targeting chemokines and/or interleukins, such as IL-6. The genomic classifiers are both associated with poor prognosis (red classification, P 1–3 and subgroup III–IV). The subgroup P 2 within the poor proliferation outcome class was found to be enriched for an ICC stem cell-like signature as well as gene signatures predicting tumor recurrence. Translational “-omics” is a rational for integrative multidimensional studies that in the future may guide the way for genomics-based clinical discoveries. A detailed representation of the combined patient subclassification is outlined, demonstrating major deregulation of oncogenic signaling pathways and driver mutations (eg, BRAF/KRAS). Activation of RTKs (eg, EGFR, HER2, MET, and VEGFR) in ICC triggers a deregulation of 2 key regulatory pathways, namely, RAS/RAF/MAPK and RAS/PI3K/AKT/mTOR, controlling cell survival and proliferation. Gastroenterology 2013 144, 687-690DOI: (10.1053/j.gastro.2013.02.018) Copyright © 2013 AGA Institute Terms and Conditions