Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches
Issued Date
2024-02-01
Resource Type
eISSN
20726694
Scopus ID
2-s2.0-85185965663
Journal Title
Cancers
Volume
16
Issue
4
Rights Holder(s)
SCOPUS
Bibliographic Citation
Cancers Vol.16 No.4 (2024)
Suggested Citation
Khosla D., Misra S., Chu P.L., Guan P., Nada R., Gupta R., Kaewnarin K., Ko T.K., Heng H.L., Srinivasalu V.K., Kapoor R., Singh D., Klanrit P., Sampattavanich S., Tan J., Kongpetch S., Jusakul A., Teh B.T., Chan J.Y., Hong J.H. Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches. Cancers Vol.16 No.4 (2024). doi:10.3390/cancers16040801 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/97459
Title
Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches
Author's Affiliation
Mazumdar Shaw Medical Center
Siriraj Hospital
Duke-NUS Medical School
Sun Yat-Sen University Cancer Center
Singapore Health Services
National Cancer Centre, Singapore
A-Star, Genome Institute of Singapore
Faculty of Medicine, Khon Kaen University
Sanjay Gandhi Postgraduate Institute of Medical Sciences
A-Star, Institute of Molecular and Cell Biology
Khon Kaen University
Postgraduate Institute of Medical Education & Research, Chandigarh
Siriraj Hospital
Duke-NUS Medical School
Sun Yat-Sen University Cancer Center
Singapore Health Services
National Cancer Centre, Singapore
A-Star, Genome Institute of Singapore
Faculty of Medicine, Khon Kaen University
Sanjay Gandhi Postgraduate Institute of Medical Sciences
A-Star, Institute of Molecular and Cell Biology
Khon Kaen University
Postgraduate Institute of Medical Education & Research, Chandigarh
Corresponding Author(s)
Other Contributor(s)
Abstract
Cholangiocarcinomas (CCA) pose a complex challenge in oncology due to diverse etiologies, necessitating tailored therapeutic approaches. This review discusses the risk factors, molecular pathology, and current therapeutic options for CCA and explores the emerging strategies encompassing targeted therapies, immunotherapy, novel compounds from natural sources, and modulation of gut microbiota. CCA are driven by an intricate landscape of genetic mutations, epigenetic dysregulation, and post-transcriptional modification, which differs based on geography (e.g., for liver fluke versus non-liver fluke-driven CCA) and exposure to environmental carcinogens (e.g., exposure to aristolochic acid). Liquid biopsy, including circulating cell-free DNA, is a potential diagnostic tool for CCA, which warrants further investigations. Currently, surgical resection is the primary curative treatment for CCA despite the technical challenges. Adjuvant chemotherapy, including cisplatin and gemcitabine, is standard for advanced, unresectable, or recurrent CCA. Second-line therapy options, such as FOLFOX (oxaliplatin and 5-FU), and the significance of radiation therapy in adjuvant, neoadjuvant, and palliative settings are also discussed. This review underscores the need for personalized therapies and demonstrates the shift towards precision medicine in CCA treatment. The development of targeted therapies, including FDA-approved drugs inhibiting FGFR2 gene fusions and IDH1 mutations, is of major research focus. Investigations into immune checkpoint inhibitors have also revealed potential clinical benefits, although improvements in survival remain elusive, especially across patient demographics. Novel compounds from natural sources exhibit anti-CCA activity, while microbiota dysbiosis emerges as a potential contributor to CCA progression, necessitating further exploration of their direct impact and mechanisms through in-depth research and clinical studies. In the future, extensive translational research efforts are imperative to bridge existing gaps and optimize therapeutic strategies to improve therapeutic outcomes for this complex malignancy.