Targeting the FOXM1 signature for early diagnosis and treatment in cholangiocarcinoma

胆管癌(CCA)是一种罕见的肝内外胆管癌。CCA的高发集中在大湄公河次区域，特别是在泰国东北部。人们对CCA的病因知之甚少，而且由于诊断较晚，治疗选择有限。研究早期诊断和有效治疗是预防该病损失的迫切需要。越来越多的证据表明，Forkhead box M1(FOXM1)转录因子在肿瘤的发生、发展、转移、血管生成和药物敏感性等方面起着关键作用。此前在泰国CCA患者组织中进行的一项基因阵列研究显示，FOXM1及其下游靶基因在几乎所有CCA患者中都上调。我们推测FOXM1在CCA的发生、发展和耐药中起关键作用。我们的目标是确定与CCA肿瘤发生、进展和药物敏感性有关的关键FOXM1基因转录信号。这不仅有助于为早期诊断和预测疾病复发寻找可靠的生物标志物，而且有助于设计针对性的治疗方法和策略，以克服CCA的耐药性。这一联合项目还将加强ICL和KKU之间的合作，并促进两个研究所的初级研究人员的职业发展。

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.