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. 2023 Mar 1;24(3):741-751.
doi: 10.31557/APJCP.2023.24.3.741.

Molecular Targets and Signaling Pathways in Cholangiocarcinoma: A Systematic Review

Rehab Idris  1 , Wanna Chaijaroenkul  1 , Kesara Na-Bangchang  1   2   3   4
Affiliations

Molecular Targets and Signaling Pathways in Cholangiocarcinoma: A Systematic Review

Rehab Idris et al. Asian Pac J Cancer Prev. .

Abstract

Background: Cholangiocarcinoma (CCA) is the second most frequent hepatobiliary cancer after hepatocellular carcinoma with a poor prognosis and limited treatment options. This study aimed to review 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.

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 pathwanys 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 sttudies that fulfilled the eligibility criteria were finally included in the analysis. The molecular biomarkers and drugs targeting signalling pathways were reported. Recent research has been focused on targeting the apoptotic and cell proliferation pathways, and in addition, the angiogenesis and metastasis pathway. More effort focused on testing the efficacy of combination therapies against the cancer cell and 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, as well as effective CCA-targeted therapies.

Keywords: EGFR; HER2; PI3K/ERK/Akt/mTOR.

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Conflict of interest statement

The authors declare no competing interests

Figures

Figure 1
Figure 1
Flow Diagram Summarizing Steps for Exclusion and Inclusion of the Research Articles Included in the Analysis
Figure 2
Figure 2
Descriptive Diagram Summarizing Signaling Pathways and Its Molecular Targets
Figure 3
Figure 3
Descriptive Diagram Summarizing Apoptosis Signaling Pathway and Molecular Targets. Reference : KEGG PATHWAY: Apoptosis - Homo sapiens (human) (genome.jp)
Figure 4
Figure 4
Descriptive Diagram Summarizing Angiogenesis Signaling Pathway and Molecular Targets
Figure 5
Figure 5
Descriptive Diagram Summarizing Metastasis Signaling Pathway and Molecular Targets. Reference: www.genome.jp
See this image and copyright information in PMC

References

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