Molecular pathogenesis of intrahepatic cholangiocarcinoma

TY - JOUR

T1 - Molecular pathogenesis of intrahepatic cholangiocarcinoma

AU - Andersen, Jesper Bøje

N1 - © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

PY - 2015/2/1

Y1 - 2015/2/1

N2 - Cholangiocarcinoma (CCA) is an orphan cancer of the hepatobiliary tract, the incidence of which has increased in the past decade. The molecular pathogenesis of this treatment-refractory disease is poorly understood. Desmoplasia is a key causal feature of CCA; however, a majority of tumors develop with no apparent etiological background. The impact of the stromal compartment on tumor progression as well as resistance to therapy is in vogue, and the epithelial-stromal crosstalk may present a target for novel treatment strategies. As such, the complexity of tumor cellularity and the molecular mechanisms underlying the diversity of growth patterns of this malignancy remain a clinical concern. It is crucial to advance our present understanding of the molecular pathogenesis of CCA to improve current clinical strategies and patient outcome. This will facilitate the delineation of patient subsets and individualization for precision therapies. Many questions persevere as to the evolutionary process and cellular origin of the initial transforming event, the context of intratumoral plasticity and the causal driver action. Next-generation sequencing has begun to underline the persistent alterations, which may be the trigger of acquired drug resistance, and the cause of metastasis and disease recurrence. A complex issue that remains is to account for the heterogeneous pool of "backseat" aberrations, which in chromosomal proximity to the causative variant are likely to influence, for example, drug response. This review explores the recent advances in defining the molecular pathways implicated in the development of this devastating disease and, which present putative clinical strategies.

AB - Cholangiocarcinoma (CCA) is an orphan cancer of the hepatobiliary tract, the incidence of which has increased in the past decade. The molecular pathogenesis of this treatment-refractory disease is poorly understood. Desmoplasia is a key causal feature of CCA; however, a majority of tumors develop with no apparent etiological background. The impact of the stromal compartment on tumor progression as well as resistance to therapy is in vogue, and the epithelial-stromal crosstalk may present a target for novel treatment strategies. As such, the complexity of tumor cellularity and the molecular mechanisms underlying the diversity of growth patterns of this malignancy remain a clinical concern. It is crucial to advance our present understanding of the molecular pathogenesis of CCA to improve current clinical strategies and patient outcome. This will facilitate the delineation of patient subsets and individualization for precision therapies. Many questions persevere as to the evolutionary process and cellular origin of the initial transforming event, the context of intratumoral plasticity and the causal driver action. Next-generation sequencing has begun to underline the persistent alterations, which may be the trigger of acquired drug resistance, and the cause of metastasis and disease recurrence. A complex issue that remains is to account for the heterogeneous pool of "backseat" aberrations, which in chromosomal proximity to the causative variant are likely to influence, for example, drug response. This review explores the recent advances in defining the molecular pathways implicated in the development of this devastating disease and, which present putative clinical strategies.

U2 - 10.1002/jhbp.155

DO - 10.1002/jhbp.155

M3 - Review

C2 - 25174625

SN - 1868-6974

JO - Journal of Hepato - Biliary - Pancreatic Sciences

JF - Journal of Hepato - Biliary - Pancreatic Sciences

ER -