Molecular Pathogenesis and Current Therapy in Intrahepatic Cholangiocarcinoma

TY - JOUR

T1 - Molecular Pathogenesis and Current Therapy in Intrahepatic Cholangiocarcinoma

AU - Høgdall, Dan Taksony Solyom

AU - O'Rourke, Colm J

AU - Taranta, Andrzej

AU - NP Oliveira, Douglas

AU - Andersen, Jesper B

N1 - © 2016 S. Karger AG, Basel.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Intrahepatic cholangiocarcinoma (iCCA) comprises one of the most rapidly evolving cancer types. An underlying chronic inflammatory liver disease that precedes liver cancer development for several decades and creates a pro-oncogenic microenvironment frequently impairs progress in therapeutic approaches. Depending on the cellular target of malignant transformation, a large spectrum of molecular and morphological patterns is observed. As such, it is crucial to advance our existing understanding of the molecular pathogenesis of iCCA, particularly its genomic heterogeneity, to improve current clinical strategies and patient outcome. This was achieved for other cancers, such as breast carcinoma, facilitated by the delineation of patient subsets and of precision therapies. In iCCA, many questions persevere as to the evolutionary process and cellular origin of the initial transforming event, the context of tumor plasticity and the causative features driving the disease. Molecular profiling and pathological techniques have begun to underline persistent alterations that may trigger inherited drug resistance (a hallmark of hepatobiliary and pancreatic cancers), metastasis and disease recurrence. In this review, we will focus on the key molecular achievements that are currently advancing the characterization and stratification of iCCA. We will discuss current clinical practice and how genomic achievements may advance diagnosis and therapy as well as ultimately improve patient outcome.

AB - Intrahepatic cholangiocarcinoma (iCCA) comprises one of the most rapidly evolving cancer types. An underlying chronic inflammatory liver disease that precedes liver cancer development for several decades and creates a pro-oncogenic microenvironment frequently impairs progress in therapeutic approaches. Depending on the cellular target of malignant transformation, a large spectrum of molecular and morphological patterns is observed. As such, it is crucial to advance our existing understanding of the molecular pathogenesis of iCCA, particularly its genomic heterogeneity, to improve current clinical strategies and patient outcome. This was achieved for other cancers, such as breast carcinoma, facilitated by the delineation of patient subsets and of precision therapies. In iCCA, many questions persevere as to the evolutionary process and cellular origin of the initial transforming event, the context of tumor plasticity and the causative features driving the disease. Molecular profiling and pathological techniques have begun to underline persistent alterations that may trigger inherited drug resistance (a hallmark of hepatobiliary and pancreatic cancers), metastasis and disease recurrence. In this review, we will focus on the key molecular achievements that are currently advancing the characterization and stratification of iCCA. We will discuss current clinical practice and how genomic achievements may advance diagnosis and therapy as well as ultimately improve patient outcome.

U2 - 10.1159/000444562

DO - 10.1159/000444562

M3 - Review

C2 - 27170400

SN - 0257-2753

VL - 34

SP - 440

EP - 451

JO - Digestive Diseases

JF - Digestive Diseases

IS - 4

ER -