Recent Advances in Understanding Cholangiocarcinoma [version 1; referees: 2 approved]

Cholangiocarcinoma (CCA) is an aggressive malignancy that arises from damaged epithelial cells, cholangiocytes, and possibly de-differentiated hepatocytes. CCA has a poor overall survival rate and limited therapeutic options. Based on this data, it is imperative that new diagnostic and therapeutic interventions be developed. Recent work has attempted to understand the pathological mechanisms driving CCA progression. Specifically, recent publications have delved into the role of cancer stem cells (CSCs), mesenchymal stem cells (MSCs), and microRNAs (miRNAs) during CCA pathology. CSCs are a specific subset of cells within the tumor environment that are derived from a cell with stem-like properties and have been shown to influence recurrence and chemoresistance during CCA. MSCs are known for their anti-inflammatory activity and have been postulated to influence malignancy during CCA, but little is known about their exact functions. miRNAs exert various functions via gene regulation at both the transcriptional and the translational levels, giving miRNAs diverse roles in CCA progression. Additionally, current miRNA-based therapeutic approaches are in clinical trials for various liver diseases, giving hope for similar approaches for CCA. However, the interactions among these three factors in the context of CCA are unknown. In this review, we focus on recently published data (within the last 3 years) that discuss the role of CSCs, MSCs, and miRNAs and their possible interactions during CCA pathogenesis