Cancer review: Cholangiocarcinoma

Abstract

Cholangiocarcinoma (CCA) is the most common biliary tract malignancy. CCA is classified as intrahepatic, perihilar or distal extrahepatic; the individual subtypes differ in their biologic behavior, clinical presentation, and management. Throughout the last decades, CCA incidence rates had significantly increased. In addition to known established risk factors, novel possible risk factors (i.e. obesity, hepatitis C virus) have been identified that are of high importance in developed countries where CCA prevalence rates have been low. CCA tends to develop on the background of inflammation and cholestasis. In recent years, our understanding of the molecular mechanisms of cholangiocarcinogenesis has increased, thereby, providing the basis for molecularly targeted therapies. In its diagnostic evaluation, imaging techniques have improved, and the role of complementary techniques has been defined. There is a need for improved CCA biomarkers as currently used ones are suboptimal. Multiple staging systems have been developed, but none of these is optimal. The prognosis of CCA is considered dismal. However, treatment options have improved throughout the last two decades for carefully selected subgroups of CCA patients. Perihilar CCA can now be treated with orthotopic liver transplantation with neoadjuvant chemoradiation achieving 5-year survival rates of 68%. Classically considered chemotherapy-resistant, the ABC-02 trial has shown the therapeutic benefit of combination therapy with gemcitabine and cisplatin. The benefits of adjuvant treatments for resectable CCA, local ablative therapies and molecularly targeted therapies still need to be defined. In this article, we will provide the reader with an overview over CCA, and discuss the latest developments and controversies.

Taurocholate Induces Cyclooxygenase-2 Expression via the Sphingosine 1-phosphate Receptor 2 in a Human Cholangiocarcinoma Cell Line

“…Impaired bile flow is often accompanied with chronic inflammation and a high basal level of COX-2 expression in the biliary tracts (1), whereas the underlying cellular mechanisms are still not fully identified. Inflammation is a key stimulator of carcinogenesis, promoting tumor cell invasion and migration in various cancers including CCA (41)(42)(43). Recently, there has been significant progress in identifying the critical role of COX-2 in tumorgenesis of various cancers including CCA (4,9,44), and PGE 2 , the enzymatic product of COX-2, has been identified as a strong promoter for mitogenesis, cell proliferation, and invasion of CCA (9,45,46).…”

MiR-490-5p Suppresses Cell Proliferation and Invasion by Targeting BUB1 in Hepatocellular Carcinoma Cells

“…Hepatocellular carcinoma (HCC) is one of the most common causes of death related to cancer worldwide, which has a remarkably lower 5-year survival rate than other categories of cancer [1,2]. HCC patients undergo various therapies such as systemic chemotherapy and liver transplantation; nevertheless, their prognoses remain poor, which is mostly due to the offensive metastasis and recurrence of HCC [3].…”

TRAIL Enhances Shikonin Induced Apoptosis through ROS/JNK Signaling in Cholangiocarcinoma Cells

“…CCA arises from varying locations within the biliary tree, classified as intrahepatic, perihilar or extrahepatic CCA [2]. The development of CCA is a multi-step process, and may be induced by sclerosing cholangitis, hepatolithiasis, parasite infections and toxins [3, 4].…”