Targeting the FOXM1 signature for early diagnosis and treatment in cholangiocarcinoma

靶向 FOXM1 特征用于胆管癌的早期诊断和治疗

• 批准号: MR/N012097/1
• 负责人: Eric Lam
• 金额: $ 45.07万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FN012097%2F1
• 关键词: Targeting; FOXM1; signature; early; diagnosis

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.

胆管癌是一种罕见的发生在肝内和肝外胆管的肿瘤。CCA的高发地区集中在大湄公河次区域，特别是在泰国东北部。对CCA的病因了解相对较少，由于诊断较晚，治疗选择有限。研究早期诊断和有效治疗是防止这种癌症损失的迫切需要。越来越多的证据表明，叉头盒M1 （FOXM1）转录因子在肿瘤的发生、进展、转移、血管生成和药物敏感性中起着关键作用。先前在泰国CCA患者组织中的基因阵列研究表明，FOXM1及其下游靶基因在几乎所有CCA病例中都上调。我们假设FOXM1在CCA的起始、发展和耐药性中起关键作用。我们的目标是确定参与CCA肿瘤发生、进展和药物敏感性的关键FOXM1基因转录特征。这不仅有助于确定可靠的生物标志物，用于早期诊断和预测疾病复发，而且有助于设计靶向治疗和策略，以克服CCA的耐药性。该合作项目还将加强ICL与KKU之间的合作，促进双方青年研究人员的职业发展。

项目成果

Tumour suppressor EP300, a modulator of paclitaxel resistance and stemness, is downregulated in metaplastic breast cancer.

肿瘤抑制因子 EP300 是紫杉醇耐药性和干性的调节剂，在化生性乳腺癌中表达下调

• DOI: 10.1007/s10549-017-4202-z
• 发表时间: 2017-06
• 期刊: Breast cancer research and treatment
• 影响因子: 3.8
• 作者: Asaduzzaman M;Constantinou S;Min H;Gallon J;Lin ML;Singh P;Raguz S;Ali S;Shousha S;Coombes RC;Lam EW;Hu Y;Yagüe E
• 通讯作者: Yagüe E

Implications of CLSPN Variants in Cellular Function and Susceptibility to Cancer.

• DOI: 10.3390/cancers12092396
• 发表时间: 2020-08-24
• 期刊: Cancers
• 影响因子: 5.2
• 作者: Azenha D;Hernandez-Perez S;Martin Y;Viegas MS;Martins A;Lopes MC;Lam EW;Freire R;Martins TC
• 通讯作者: Martins TC

Targeting SPINK1 in the damaged tumour microenvironment alleviates therapeutic resistance.

靶向受损肿瘤微环境中的 SPINK1 可减轻治疗耐药性

• DOI: 10.1038/s41467-018-06860-4
• 发表时间: 2018-10-17
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Chen F;Long Q;Fu D;Zhu D;Ji Y;Han L;Zhang B;Xu Q;Liu B;Li Y;Wu S;Yang C;Qian M;Xu J;Liu S;Cao L;Chin YE;Lam EW;Coppé JP;Sun Y
• 通讯作者: Sun Y