Targeting the FOXM1 signature for early diagnosis and treatment in cholangiocarcinoma

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Cholangiocarcinoma (CCA) is rare cancer of the intrahepatic and extra hepatic bile ducts. High incidences of CCA are clustered in the Greater Mekong sub-region, particularly in the northeast of Thailand. Relatively little is known about the cause of CCA, and the treatment options are limited because of late diagnosis. Researching for early diagnosis and effective treatment is an urgent need to prevent the loss from this cancer. Accumulating evidence indicates that the Forkhead box M1 (FOXM1) transcription factor has a key role in tumour initiation, progression, metastasis, angiogenesis and drug sensitivity. A previous gene array study in Thai CCA patient tissues has revealed that FOXM1 and its downstream targets as genes upregulated in almost all CCA cases. We hypothesise that FOXM1 plays a key role in CCA initiation, development and drug resistance. We aim to identify the critical FOXM1 gene transcription signatures involved in CCA tumorigenesis, progression and drug sensitivity. This will not only help to identify reliable biomarkers for early diagnosis and for predicting disease relapse but also aid the design of targeted therapies and strategies to overcome drug resistance in CCA. This joint project will also strengthen the collaborations between ICL and KKU, and promote the career development of junior researchers from both institutes.