Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches
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 the...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/4/801 |
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| author | Divya Khosla Shagun Misra Pek Lim Chu Peiyong Guan Ritambhra Nada Rajesh Gupta Khwanta Kaewnarin Tun Kiat Ko Hong Lee Heng Vijay Kumar Srinivasalu Rakesh Kapoor Deepika Singh Poramate Klanrit Somponnat Sampattavanich Jing Tan Sarinya Kongpetch Apinya Jusakul Bin Tean Teh Jason Yongsheng Chan Jing Han Hong |
| author_facet | Divya Khosla Shagun Misra Pek Lim Chu Peiyong Guan Ritambhra Nada Rajesh Gupta Khwanta Kaewnarin Tun Kiat Ko Hong Lee Heng Vijay Kumar Srinivasalu Rakesh Kapoor Deepika Singh Poramate Klanrit Somponnat Sampattavanich Jing Tan Sarinya Kongpetch Apinya Jusakul Bin Tean Teh Jason Yongsheng Chan Jing Han Hong |
| author_sort | Divya Khosla |
| collection | DOAJ |
| description | 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 <i>FGFR2</i> gene fusions and <i>IDH1</i> 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. |
| first_indexed | 2024-03-07T22:39:15Z |
| format | Article |
| id | doaj.art-fba92e29db7c4b5fb94759ca636ebf0d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-07T22:39:15Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-fba92e29db7c4b5fb94759ca636ebf0d2024-02-23T15:11:17ZengMDPI AGCancers2072-66942024-02-0116480110.3390/cancers16040801Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic ApproachesDivya Khosla0Shagun Misra1Pek Lim Chu2Peiyong Guan3Ritambhra Nada4Rajesh Gupta5Khwanta Kaewnarin6Tun Kiat Ko7Hong Lee Heng8Vijay Kumar Srinivasalu9Rakesh Kapoor10Deepika Singh11Poramate Klanrit12Somponnat Sampattavanich13Jing Tan14Sarinya Kongpetch15Apinya Jusakul16Bin Tean Teh17Jason Yongsheng Chan18Jing Han Hong19Department of Radiotherapy and Oncology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, IndiaDepartment of Radiotherapy and Oncology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, IndiaCancer and Stem Cell Biology Programme, Duke-NUS Medical School, Singapore 169857, SingaporeGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore 138672, SingaporeDepartment of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, IndiaDepartment of GI Surgery, HPB, and Liver Transplantation, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, IndiaSingHealth Duke-NUS Institute of Biodiversity Medicine, Singapore 168583, SingaporeCancer Discovery Hub, National Cancer Center Singapore, Singapore 168583, SingaporeLaboratory of Cancer Epigenome, Division of Medical Science, National Cancer Center Singapore, Singapore 168583, SingaporeDepartment of Medical Oncology, Mazumdar Shaw Medical Center, NH Health City Campus, Bommasandra, Bangalore 560099, IndiaDepartment of Radiotherapy and Oncology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, IndiaSingHealth Duke-NUS Institute of Biodiversity Medicine, Singapore 168583, SingaporeCholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen 40002, ThailandSiriraj Center of Research Excellence for Systems Pharmacology, Department of Pharmacology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 73170, ThailandLaboratory of Cancer Epigenome, Division of Medical Science, National Cancer Center Singapore, Singapore 168583, SingaporeCholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, ThailandCholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, ThailandCancer and Stem Cell Biology Programme, Duke-NUS Medical School, Singapore 169857, SingaporeCancer Discovery Hub, National Cancer Center Singapore, Singapore 168583, SingaporeCancer and Stem Cell Biology Programme, Duke-NUS Medical School, Singapore 169857, SingaporeCholangiocarcinomas (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 <i>FGFR2</i> gene fusions and <i>IDH1</i> 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.https://www.mdpi.com/2072-6694/16/4/801cholangiocarcinomatherapeutic approachespathobiology |
| spellingShingle | Divya Khosla Shagun Misra Pek Lim Chu Peiyong Guan Ritambhra Nada Rajesh Gupta Khwanta Kaewnarin Tun Kiat Ko Hong Lee Heng Vijay Kumar Srinivasalu Rakesh Kapoor Deepika Singh Poramate Klanrit Somponnat Sampattavanich Jing Tan Sarinya Kongpetch Apinya Jusakul Bin Tean Teh Jason Yongsheng Chan Jing Han Hong Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches Cancers cholangiocarcinoma therapeutic approaches pathobiology |
| title | Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches |
| title_full | Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches |
| title_fullStr | Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches |
| title_full_unstemmed | Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches |
| title_short | Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches |
| title_sort | cholangiocarcinoma recent advances in molecular pathobiology and therapeutic approaches |
| topic | cholangiocarcinoma therapeutic approaches pathobiology |
| url | https://www.mdpi.com/2072-6694/16/4/801 |
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