Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches

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Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches
Title:
Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches
Journal Title:
Cancers
Publication Date:
16 February 2024
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. (2024). Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches. Cancers, 16(4), 801. https://doi.org/10.3390/cancers16040801
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.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
This research / project is supported by the Agency for Science, Technology and Research (A*STAR) - Singapore Therapeutics Development Review Pre-Pilot
Grant Reference no. : H23G1a0009

This research / project is supported by the Ministry of Health, National Medical Research Council (NMRC) - Research Transition Award
Grant Reference no. : TA21jun-0005

This research / project is supported by the SingHealth - AM/ACP-Designated Philanthropic Fund Grant Award
Grant Reference no. : 08/FY2023/EX/27-A65

This research / project is supported by the Ministry of Health, National Medical Research Council (NMRC) - Singapore Translational Research Investigator Award
Grant Reference no. : MOH-000248-00

This research / project is supported by the Ministry of Health, National Medical Research Council (NMRC) - Open Fund—Individual Research Grant
Grant Reference no. : MOH-000144, COVID19TUG21-0146

This research / project is supported by the A*STAR-AMED - A*STAR-AMED Joint Grant
Grant Reference no. : 236B9008
Description:
ISSN:
2072-6694