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

食道癌和与胃交界处的癌症是全世界癌症死亡率的第六大常见原因。在英国，这种癌症的发病率在过去30年中增加了6倍，并且由于诊断晚，结果很差，只有不到20%的人活了5年以上。另一方面，我们有机会及早发现这些癌症，并防止其发展为危及生命的疾病，因为它们是在数年内从癌前阶段逐渐发展起来的。我们迄今为止的一个工作例子是开发Cytosponge取样装置和实验室测试。（称为TFF 3），可用于胃灼热患者，他们有患癌前疾病巴雷特食管的风险。Cytosponge现已获得CE认证，并已上市，其临床试验数据支持其使用和NHS实施计划。未来五年的关键目标是更好地了解为什么突变在食管和胃细胞中积累，使癌症更容易发展。我们想了解这些癌症的发展是否有不止一个起源细胞，或者它是否是一种具有不同亚型的疾病，每种亚型都有不同的预后。我们将开发临床预测模型，以确定巴雷特患者是否可能有一个惰性或侵略性的路径，然后将其应用于Cytosponge样本，并结合先进的内窥镜成像技术。Fitzgerald团队高度协作，包括具有一系列专业知识的临床医生和科学家。通过附近的临床研究机构，我们拥有最先进的内窥镜设备，可以将我们的发现转化为临床试验。总之，我们计划开展一项雄心勃勃的计划，为临床试验提供桥梁，以改善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.