Potential targeted therapy for liver fluke associated cholangiocarcinoma
Kulthida Vaeteewoottacharn1, Wunchana Seubwai, Vajarabhongsa Bhudhisawasdi
1Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 123 Mitraparb Road, Khon Kaen, 40002, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
Abstract:
Biliary tree cancer or cholangiocarcinoma (CCA) is an unusual subtype of liver cancer with exceptionally poor prognosis. Lack of specific symptoms and availability of early diagnostic markers account for late diagnosis of CCA. Surgical treatment is a gold standard choice but few patients are candidates and local recurrence after surgery is high. Benefit of systemic chemotherapy is limited; hence, better treatment options are required. The differences in etiology, anatomical positions and pathology make it difficult to generalize all CCA subtypes for a single treatment regimen. Herein, we review the uniqueness of molecular profiling identified by multiple approaches, for example, serial analysis of gene expression, exome sequencing, transcriptomics/proteomics profiles, protein kinase profile, etc., that provide the opportunity for treatment of liver fluke-associated CCA. Anti-inflammatory, immunomodulator/immunosuppressor, epidermal growth factor receptor or platelet-derived growth factor receptor inhibitors, multi-targeted tyrosine kinase inhibitor, IL6 antagonist, nuclear factor-κB inhibitor, histone modulator, proteasome inhibitor as well as specific inhibitors suggested from various study approaches, such as MetAP2 inhibitor, 1,25(OH)2 D3 and cyclosporine A are suggested in this review for the treatments of this specific CCA subtype. This might provide an alternative treatment option for CCA patients; however, clinical trials in this specific CCA group are required.
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