Electrochemical Profiling of Extracellular Vesicles (EP4EVs)

战胜癌症的关键在于早期发现，从而能够更快地获得更好的治疗，以提高长期生存率。在英国，每年约有55，000名女性和370名男性被诊断患有乳腺癌（BC）。虽然大多数癌症病例在早期阶段被诊断出来，但在英国，“两周等待”是诊断癌症的最常见途径，其次是“31天等待”决定治疗。英国每个病例至少花费7，247英镑，每年用于BC诊断/治疗的费用总计2.43亿英镑。因此，开发高灵敏度和具有成本效益的诊断和监测系统，使用小样本量进行快速癌症诊断和诊断（减少诊断/治疗时间）是英国个性化医疗的关键战略优先事项。局部晚期或侵袭性乳腺癌的标准治疗是新辅助化疗（NACT），然后进行乳腺手术。目前，NACT疗效的术前评估是基于医学成像技术，如磁共振成像（MRI）或计算机断层扫描（CT），然而，这些成像技术在监测治疗反应方面的灵敏度降低，不能用于预测疾病进展。2本项目旨在开发电化学分析作为液体活检试验（简单的血液测试）以通过检测从BC细胞释放的肿瘤衍生的细胞外囊泡（tdEV）上的BC特异性表面蛋白来评估NACT的功效。这涉及通过整合表面化学与特异性抗体来开发电化学测定，以检测临床相关浓度的临床相关tdEV表面蛋白。在这里，我们建议证明一个可行性研究，涉及测试这些电化学检测的实时电化学分析的tdEV表面蛋白的血液样本中获得的BC患者收集在不同阶段的NACT。该多学科项目将通过与我们在热那亚大学的国际合作伙伴（专业知识-内科），爱丁堡大学（癌症肿瘤学家）和斯旺西大学（细胞外囊泡生物学家）的英国共同研究者以及英国工业合作伙伴（传感器制造商）的战略合作伙伴关系进行交付。该项目的成功将有助于扩大基于快速和高通量液体活检的癌症诊断和诊断学，从而减少诊断/治疗时间和成本，这将直接影响英国和全球的医疗保健行业。

Beating Cancer is all about early detection, which enables faster access to better treatment to improve long-term survival rates. Around 55,000 women and 370 men are diagnosed with breast cancer (BC) every year in the UK. Although most cancer cases are diagnosed at an early stage, a "two-week wait" is the most common route to diagnosing cancer in UK that is followed by a "31-day wait" for a decision to treat. The UK spends at least £7,247 per case and a total of £243 million per year for BC diagnosis/treatment. Thus, developing highly sensitive and cost-effective diagnostic and monitoring systems using small sample volumes for rapid cancer diagnostics and prognostics (reducing diagnosis/treatment times) is a key UK-wide strategic priority in personalised medicine. The standard of care for locally advanced or aggressive BC is neoadjuvant chemotherapy (NACT) followed by breast surgery. Currently, the pre-surgical assessment of the efficacy of NACT is based on medical imaging techniques such as magnetic resonance imaging (MRI), or computerized tomography scan (CT), however, these imaging techniques suffer from a reduced sensitivity in monitoring treatment response and cannot be used for the prediction of disease progression.This project aims at developing electrochemical profiling as a liquid-biopsy test (simple blood test) to access the efficacy of NACT through detecting the BC specific surface proteins on the tumour derived extracellular vesicles (tdEVs) released from the BC cells. This involves the development of electrochemical assays through integration of surface chemistries with specific antibodies to detect clinically relevant tdEVs surface proteins at clinically relevant concentrations. Here, we propose to demonstrate a feasibility study that involves the testing of these electrochemical assays for the real-time electrochemical profiling of tdEVs surface proteins in blood samples obtained from the BC patients collected at different stages of NACT. This multidisciplinary project will be delivered through strategic partnership with our international partner at University of Genova (expertise - internal medicine), UK co-Investigators at University of Edinburgh (cancer oncologist) and Swansea University (extracellular vesicles biologist) and Industrial partners in UK (sensor manufacturer). The success of this project will assist the expansion of rapid and high throughput liquid-biopsy based cancer diagnostics and prognostics and thus, would reduce the diagnosis/treatment time and cost, which will directly impact the healthcare sector in UK and worldwide.