Biomarker Development in Cancer- Bridging the Translational Gap

癌症生物标志物的开发——弥合转化差距

• 批准号: MR/W003589/1
• 负责人: Richard Turkington
• 金额: $ 21.25万
• 依托单位: Queen's University Belfast
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW003589%2F1
• 关键词: Biomarker; Development; Cancer; Bridging; Translational

Every cancer is different and standard treatments such as chemotherapy work better for some patients compared to others. The ability to match the right patient to the right treatment would enable cancer doctors to give patients the cancer drugs with the best chance of working. This idea is called 'personalised' or 'precision' oncology and will lead to tailored treatment plans for each patient. Pre-selection of patients will also benefit the pharmaceutical industry by increasing the chance of a successful clinical trial and subsequent cancer drug approval. For precision oncology to be realised in the clinical setting accurate tests, or biomarkers, are needed which can use the genetic features of a patient's tumour to assist in determining the optimal treatment strategy.Historically, developing a cancer biomarker has been difficult. Despite thousands of potential tests only a select few have made it through to day-to-day use in hospitals; there are many reasons for this. Cancer biomarkers developed in a university setting may not produce reliable results when used in hospital laboratories. This could be due to inaccuracies in how they were designed or insufficient laboratory procedures to limit variation between batches of tests or different laboratories. Also, many biomarkers are developed using impractical technologies which are not used in hospital laboratories, do not provide clinically relevant results or are not produced or tested to a high enough standard to gain government approval for use. To overcome these issues collaboration between universities, hospitals and the biotechnology industry is needed. More importantly, there are very few cancer physicians with the knowledge and skills required to design these tests and work in all of these settings. This proposal seeks to break down these barriers and develop a new, collaborative approach to cancer biomarker development. By becoming a UKRI Innovation Scholar, Dr Turkington will gain essential skills in the design and development of cancer biomarkers. During his secondment at Almac Diagnostic Services (ADS) he will learn how to manage cancer biomarker tests as part of clinical trials. He will gain experience of a high-level commercial environment as well as essential skills in management and leadership. This knowledge will be transferred back to Queen's University Belfast (QUB) and used to progress research biomarkers, design new cancer treatment strategies and influence the wider research culture. Dr Turkington will also be integral to the design of new cancer biomarkers and clinical trials, which will be tested through UKRI and UK government funded regional cancer trial programmes.Northern Ireland already has a strong health innovation environment with the presence of QUB, five research-active Healthcare Trusts and multiple biotechnology companies, including ADS, who specialise in clinical biomarker development and delivery. Over several years QUB has positioned itself as a leader in precision oncology through investments such as the Precision Medicine Centre of Excellence (PMC) and NI Biobank. The PMC is supported by the UKRI/Innovate UK Industrial Strategy Challenge Fund to use artificial intelligence to select chemotherapy for patients. Combined with the recent submission for UKRI Strength in Places funding to create the NI Precision Biomarkers and Therapeutics Consortium (NIPBT) and the UK government funded Belfast Region City Deal 'Institute of Research Excellence for Advanced Clinical Healthcare' (iREACH), Northern Ireland is rapidly developing a dynamic ecosystem for precision medicine. In summary, this scholarship will benefit ADS and QUB through the sharing of expertise and will also develop Dr Turkington into a uniquely skilled individual who can drive innovation in precision oncology. It will benefit the wider healthcare infrastructure in Northern Ireland and cancer patients by providing effective, precise and tailored treatment.

每种癌症都是不同的，与其他癌症相比，标准治疗，如化疗，对某些患者效果更好。将合适的患者与合适的治疗相匹配的能力将使癌症医生能够给患者提供最有可能奏效的抗癌药物。这一想法被称为“个性化”或“精确”肿瘤学，将导致为每个患者量身定做治疗计划。患者的预选也将增加成功的临床试验和随后的抗癌药物批准的机会，从而使制药业受益。为了在临床环境中实现精确的肿瘤学，需要准确的测试或生物标记物，可以使用患者肿瘤的遗传特征来帮助确定最佳治疗策略。从历史上看，开发癌症生物标记物一直是困难的。尽管有数以千计的潜在测试，但只有几个精挑细选的人进入了医院的日常使用；原因很多。在大学环境下开发的癌症生物标记物在医院实验室使用时可能不会产生可靠的结果。这可能是因为它们的设计不准确，或者实验室程序不足以限制不同批次测试或不同实验室之间的差异。此外，许多生物标记物是使用不切实际的技术开发的，这些技术没有在医院实验室使用，没有提供临床相关的结果，或者没有生产或测试到足够高的标准来获得政府批准使用。要解决这些问题，需要大学、医院和生物技术行业之间的合作。更重要的是，很少有癌症医生拥有设计这些测试并在所有这些环境中工作所需的知识和技能。这项提议寻求打破这些障碍，并开发一种新的、合作的方法来开发癌症生物标记物。通过成为UKRI创新学者，特金顿博士将获得设计和开发癌症生物标记物的基本技能。在他借调到Almac诊断服务公司(ADS)期间，他将学习如何将癌症生物标记物测试作为临床试验的一部分进行管理。他将获得高水平商业环境的经验，以及管理和领导方面的基本技能。这些知识将传回贝尔法斯特女王大学(QUB)，用于发展研究生物标记物，设计新的癌症治疗策略，并影响更广泛的研究文化。特金顿博士还将参与新的癌症生物标记物和临床试验的设计，这些试验将通过UKRI和英国政府资助的地区性癌症试验计划进行测试。北爱尔兰已经拥有强大的健康创新环境，有QUB、五个研究活跃的医疗信托基金和包括ADS在内的多家生物技术公司，这些公司专门从事临床生物标记物的开发和交付。几年来，昆士兰大学通过精准医学卓越中心(PMC)和NI Biobank等投资，将自己定位为精准肿瘤学领域的领导者。PMC得到了UKRI/Innovate UK产业战略挑战基金的支持，利用人工智能为患者选择化疗。北爱尔兰最近提交了UKRI Strong in Places资金申请，以创建NI Precision Biomarkers and Treeutics Consortium(NIPBT)和英国政府资助的贝尔法斯特地区市交易“高级临床医疗卓越研究学院”(IReach)，北爱尔兰正在迅速发展一个充满活力的精准医学生态系统。总而言之，这项奖学金将通过分享专业知识使ADS和昆士兰大学受益，还将把特金顿博士培养成一名能够推动精确肿瘤学创新的独特技能个人。它将通过提供有效、精确和量身定制的治疗，使北爱尔兰更广泛的医疗基础设施和癌症患者受益。

项目成果

Mismatch Repair and Microsatellite Instability Testing for Immune Checkpoint Inhibitor Therapy: ASCO Endorsement of College of American Pathologists Guideline.

免疫检查点抑制剂治疗的错配修复和微卫星不稳定性测试：美国病理学家学会指南的 ASCO 认可。

• DOI: 10.1200/jco.22.02462
• 发表时间: 2023
• 期刊: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
• 作者: Vikas,Praveen;Messersmith,Hans;Compton,Carolyn;Sholl,Lynette;Broaddus,RussellR;Davis,Anjee;Estevez-Diz,Maria;Garje,Rohan;Konstantinopoulos,PanagiotisA;Leiser,Aliza;Mills,AnneM;Norquist,Barbara;Overman,MichaelJ;Sohal,Davendra
• 通讯作者: Sohal,Davendra