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（CCA）是肝内和肝外胆管的罕见癌症。 CCA的高发病率聚集在更大的湄公河区域，尤其是在泰国东北部。关于CCA的原因，知之甚少，由于诊断晚期，治疗方案受到限制。进行早期诊断和有效治疗的研究迫切需要防止这种癌症丧失。积累的证据表明，叉子盒M1（FOXM1）转录因子在肿瘤起始，进展，转移，血管生成和药物敏感性中具有关键作用。先前在泰国CCA患者组织中的基因阵列研究表明，在几乎所有CCA病例中，FOXM1及其下游靶标都上调。我们假设FOXM1在CCA启动，发育和耐药性中起关键作用。我们旨在确定与CCA肿瘤发生，进展和药物敏感性有关的临界FOXM1基因转录特征。这不仅将有助于确定可靠的生物标志物来早期诊断和预测疾病复发，还有助于设计有针对性的疗法和克服CCA耐药性的策略。该联合项目还将加强ICL和KKU之间的合作，并促进两家研究所的初级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