Cholangiocarcinoma: Molecular Abnormalities and Cells of Origin

Abstract

Cholangiocarcinomas (CCAs) are a group of heterogeneous epithelial malignancies that can originate at the level of any location of the biliary tree. These tumors are relatively rare but associated with a high rate of mortality. CCAs are morphologically and molecularly heterogeneous and for their location can be distinguished as intracellular and extracellular, subdivided into perihilar and distal. Recent epidemiological, molecular, and cellular studies have supported that the consistent heterogeneity observed for CCAs may result from the convergence of various key elements mainly represented by risk factors, heterogeneity of the associated molecular abnormalities at genetic and epigenetic levels and by different potential cells of origin. These studies have consistently contributed to better defining the pathogenesis of CCAs and to identify in some instances new therapeutic targets. Although the therapeutic progress were still limited, these observations suggest that a better understanding of the molecular mechanisms underlying CCA in the future will help to develop more efficacious treatment strategies.

Identification of neutrophil‐related genes and development of a prognostic model for cholangiocarcinoma

“…Cholangiocarcinoma (CCA), also known as bile duct cancer, is a rare and aggressive malignancy that arises from the epithelial cells of the bile ducts. 1 It accounts for approximately 3% of all gastrointestinal malignancies, and its incidence has been steadily increasing over the past few decades. 2 Despite advances in diagnosis and treatment, the overall prognosis of CCA remains poor, with a 5 year survival rate of less than 10%.…”

Tumor Microenvironment Remodeling in Gastrointestinal Cancer: Role of miRNAs as Biomarkers of Tumor Invasion

“…They share similarities but also have important differences that can affect the pathogenesis and outcome. Although this anatomical classification is widely used, other factors such as tumor growth pattern and cell of origin (cholangiocytes, perishable glands, liver progenitor cells, or hepatocytes) provide alternative methods of classification that can better predict tumor behavior [ 20 ]. Patients with CCA are often asymptomatic in the early stages of the tumor, and, for most of them, diagnosis occurs at an advanced stage.…”