Treatment of Intrahepatic Cholangiocarcinoma—A Multidisciplinary Approach

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Cholangiocarcinoma (CCA) is the second most common primary liver cancer and subsumes a heterogeneous group of malignant tumors arising from the intra- or extrahepatic biliary tract epithelium. A rising mortality from CCA has been reported worldwide during the last decade, despite significant improvement of surgical and palliative treatment. Over 50% of CCAs originate from proximal extrahepatic bile ducts and constitute the most common CCA entity in the Western world. Clinicopathological characteristics such as lymph node status and poor differentiation remain the best-studied, but imperfect prognostic factors. The identification of prognostic molecular markers as an adjunct to traditional staging systems may not only facilitate the selection of patients who would benefit the most from surgical, adjuvant or palliative treatment strategies, but may also be helpful in defining the aggressiveness of the disease and identifying patients at high-risk for tumor recurrence. The purpose of this review is to provide an overview of currently known molecular prognostic and predictive markers and their role in CCA.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prognostic and Predictive Molecular Markers in Cholangiocarcinoma

Pavicevic

Reichelt

Uluk

et al. 2022

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“…In particularly difficult cases, as for certain types of HCCs as well as combined hepatocellular-cholangiocarcinoma (HCC-CCC), the diagnosis needs further immunohistochemical analyses such as Hepatocyte paraffin 1 (HepPar1) [24]. So far, the final histopathologic diagnosis of iCCA including its subtype is necessary for further therapy planning, even in unresectable cases [25]. Tumor biologic heterogeneity is reflected in the new classification of subtypes, which incorporates a large number of different diagnostic factors.…”

Section: Discussionmentioning

confidence: 99%

Integrative Analysis of Intrahepatic Cholangiocarcinoma Subtypes for Improved Patient Stratification: Clinical, Pathological, and Radiological Considerations

Gerber

Müller

Bartsch

et al. 2022

Intrahepatic cholangiocarcinomas (iCCAs) may be subdivided into large and small duct types that differ in etiology, molecular alterations, therapy, and prognosis. Therefore, the optimal iCCA subtyping is crucial for the best possible patient outcome. In our study, we analyzed 148 small and 84 large duct iCCAs regarding their clinical, radiological, histological, and immunohistochemical features. Only 8% of small duct iCCAs, but 27% of large duct iCCAs, presented with initial jaundice. Ductal tumor growth pattern and biliary obstruction were significant radiological findings in 33% and 48% of large duct iCCAs, respectively. Biliary epithelial neoplasia and intraductal papillary neoplasms of the bile duct were detected exclusively in large duct type iCCAs. Other distinctive histological features were mucin formation and periductal-infiltrating growth pattern. Immunohistochemical staining against CK20, CA19-9, EMA, CD56, N-cadherin, and CRP could help distinguish between the subtypes. To summarize, correct subtyping of iCCA requires an interplay of several factors. While the diagnosis of a precursor lesion, evidence of mucin, or a periductal-infiltrating growth pattern indicates the diagnosis of a large duct type, in their absence, several other criteria of diagnosis need to be combined.

“…Nowadays, CCA is a fatal cancer, with a survival rate beyond a year of diagnosis inferior to 5% [ 184 ]. Therapeutic options are limited and surgery is the cornerstone of cure for CCA, even though most patients present with locally advanced or metastatic disease [ 185 ]. In the past few years, druggable alterations such as fibroblast growth factor receptor 2 (FGFR2) gene fusions and rearrangements, or isocitrate dehydrogenase-1 (IDH-1) and BRAF mutations, have been widely described in CCA patients, further indicating the important differences between iCCA and PCC/DCC, as thoroughly reviewed in [ 186 ].…”

Section: Hur and Hepatobiliary Cancersmentioning

confidence: 99%

Hu Antigen R (HuR) Protein Structure, Function and Regulation in Hepatobiliary Tumors

Lachiondo‐Ortega

Delgado

Baños-Jaime

et al. 2022

Hu antigen R (HuR) is a 36-kDa ubiquitous member of the ELAV/Hu family of RNA-binding proteins (RBPs), which plays an important role as a post-transcriptional regulator of specific RNAs under physiological and pathological conditions, including cancer. Herein, we review HuR protein structure, function, and its regulation, as well as its implications in the pathogenesis, progression, and treatment of hepatobiliary cancers. In particular, we focus on hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), tumors where the increased cytoplasmic localization of HuR and activity are proposed, as valuable diagnostic and prognostic markers. An overview of the main regulatory axes involving HuR, which are associated with cell proliferation, invasion, metastasis, apoptosis, and autophagy in HCC, is provided. These include the transcriptional, post-transcriptional, and post-translational modulators of HuR function, in addition to HuR target transcripts. Finally, whereas studies addressing the relevance of targeting HuR in CCA are limited, in the past few years, HuR has emerged as a potential therapeutic target in HCC. In fact, the therapeutic efficacy of some pharmacological inhibitors of HuR has been evaluated, in early experimental models of HCC. We, further, discuss the major findings and future perspectives of therapeutic approaches that specifically block HuR interactions, either with post-translational modifiers or cognate transcripts in hepatobiliary cancers.