Signaling Pathways and Molecular Targets in Cholangiocarcinoma

Background: The article systematically reviewed existing knowledge on the genetic basis of CCA, molecular targets/signaling pathways involved in the pathogenesis, disease progression and prognosis, including potential targets for targeted therapies of CCA. Cholangiocarcinoma (CCA) is the second most frequent hepatobiliary cancer after hepatocellular carcinoma with a poor prognosis and limited treatment options.

Methods: The systematic review was performed in compliance with PRISMA guidelines. A systematic search in PubMed and Science Direct databases was performed using the following keywords: “cholangiocarcinoma”, AND “molecular target” AND/OR “signaling pathway”, AND/OR “targeted therapy”, AND/OR “cancer chemotherapy.” The eligibility criteria included: i) full-text articles published in English, ii) articles with in vitro and/or in vivo and/or clinical studies of molecular targets/signaling pathways related to CCA pathogenesis/disease progression/prognosis and/or targeted therapy. Seventy-three studies that fulfilled the eligibility criteria were finally included in the final data synthesis.

Results: A total of 833 relevant articles published up to April 2022 were identified and 73 studies that fulfilled the eligibility criteria were finally included in the analysis. The molecular biomarkers and drugs targeting signalling pathways were reported. Recent research has focused on targeting the apoptotic and cell proliferation pathways and the angiogenesis and metastasis pathways. More effort focused on testing the efficacy of combination therapies against cancer cells, specifically CCA. The PI3K (Phosphoinositide 3-kinases)/ERK/Akt (AKT serine/threonine kinase 1)/mTOR (mammalian target of rapamycin) signaling pathway and HER2 (Human epidermal growth factor receptor 2) and EGFR (Epidermal Growth Factor Receptor) pathways are the most potential targets for CCA therapy.

Conclusion: The information obtained could be exploited for further development of diagnostic tools for early diagnosis of CCA and effective CCA-targeted therapies.