A translational programme to elucidate the pathophysiology of oesophago-gastric cancer and develop clinical innovations

食道癌(食道癌)和与胃交界处的癌症是全世界癌症死亡的第六大常见原因。在英国，这种类型的癌症的发病率在过去30年里增加了6倍，结果很差，只有不到20%的人因为诊断晚了而活了5年以上。另一方面，有机会及早发现这些癌症并防止进展为危及生命的疾病，因为它们是在一段时间内从癌前阶段逐渐发展起来的。到目前为止，我们工作的一个例子是开发了细胞学采样设备和实验室测试(称为TFF3)，可以给有癌前疾病风险的胃灼热患者Barrett‘s食道。CytSponge现在已获得CE标志，并可在商业上获得令人信服的临床试验数据，以支持其使用和NHS的实施计划。未来五年的关键目标是更好地了解为什么突变会在食道和胃的细胞中积累，从而使癌症更有可能发展。我们想要了解这些癌症的发展是否有不止一个起源细胞，或者是否是一种具有不同亚型的疾病，每种疾病都有不同的预后。我们将开发临床预测模型，以确定Barrett‘s患者可能具有惰性或侵略性路径，然后将其应用于CytSponge样本，并结合复杂的内窥镜成像技术。Fitzgerald小组高度合作，包括具有一系列专业知识的临床医生和科学家。我们处于通过附近的临床研究机构和最先进的内窥镜设备将我们的发现转化为临床试验的理想位置。总而言之，我们计划一个雄心勃勃的计划，将提供一座通往临床试验的桥梁，以改进对这种侵袭性癌症的管理策略。

Cancers of the gullet (oesophagus) and at the junction with the stomach are the sixth most common cause of cancer mortality worldwide. In the UK rates of this cancer type have increased 6-fold in the past 30 years and the outcomes are poor with fewer than 20% living beyond 5 years because of late diagnosis. On the other hand, there is the opportunity to detect these cancers early and prevent progression to life-threatening disease because they develop gradually from pre-cancerous stages over a period of years.One example of our work to date has been the development of the Cytosponge sampling device and laboratory test (called TFF3) which can be given to patients with heartburn, who are at risk of the pre-cancerous condition Barrett's oesophagus. Cytosponge is now CE marked and commercially available with compelling clinical trial data to support its use and plans for NHS implementation.The key aims in the next five years are to better understand why mutations accumulate in cells of the oesophagus and stomach that make cancer more likely to develop. We would like to understand whether there is more than one cell of origin for the development of these cancers or whether it is one type of disease with different sub-types that each have a different prognosis. We will develop clinical prediction models to determine whether patients with Barrett's are likely to have an indolent or an aggressive path and then apply this to Cytosponge samples and incorporate sophisticated endoscopy imaging techniques. The Fitzgerald group is highly collaborative and includes clinicians and scientists with a range of expertise. We are ideally placed to translate our findings into clinical trials through the nearby Clinical Research Facility with state-of-the-art endoscopy equipment.In summary, we plan an ambitious programme that will provide a bridge to clinical trials to improve management strategies for this aggressive cancer.