MicroSNARE: Automated Enrichment Of Circulating Tumour DNA For Improved Cancer Treatment

MicroSNARE：自动富集循环肿瘤 DNA 以改善癌症治疗

• 批准号: EP/Y023153/1
• 负责人: Nick Leslie
• 金额: $ 96.58万
• 依托单位: Heriot-Watt University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FY023153%2F1
• 关键词: MicroSNARE; Automated; Enrichment; Circulating; Tumour

Currently, in order to select their best treatment options, most cancer patients need to have an unpleasant and expensive surgical operation to remove a sample of tissue from their tumour, called a biopsy. However, all people have small amounts of DNA circulating freely in their blood (which is not inside their blood cells) and in cancer patients some of this circulating free DNA has come from their tumour. This tumour DNA is different from their healthy circulating DNA as it carries the mutations which have transformed these cells from healthy cells to cancer cells. Therefore this circulating tumour DNA (ctDNA) has the potential to reveal details about the patient's cancer and show which treatments are most likely to be successful. Methods to study ctDNA have been developed but all are limited by the low abundance of ctDNA and the presence of larger amounts of background healthy DNA in blood samples. Our proposal is to develop methods to process blood samples, degrading healthy DNA sequences and by enriching the informative tumour DNA, making it easier to detect and characterise. We have developed a new method (SNARE) which we wish to test against an existing promising enrichment method (NaME-PrO). The widespread use of these methods to benefit patients will require their automation, which we will develop in both robotic benchtop and microfluidic platforms. Finally, we will quantitatively assess the best performing methods using a set of blood samples from breast cancer patients, which should give more sensitive detection of the ctDNA in these samples and require less expensive DNA sequencing. In summary, the project should help make successful analysis of cancer patient's blood samples cheaper and more reliable, so reducing the number of biopsy operations that are required and enabling more evidence-based cancer therapy.

目前，为了选择其最佳治疗选择，大多数癌症患者需要进行不愉快且昂贵的手术手术，以从其肿瘤中清除组织样本，称为活检。但是，所有人都有少量的DNA在血液中自由循环（不在血细胞内），而在癌症患者中，其中一些循环的自由DNA来自其肿瘤。该肿瘤DNA与它们的健康循环DNA不同，因为它带有从健康细胞转变为癌细胞的突变。因此，这种循环肿瘤DNA（CTDNA）有可能揭示有关患者癌症的细节，并显示哪些治疗最有可能成功。已经开发了研究ctDNA的方法，但所有方法都受到ctDNA的含量低的限制，并且在血液样本中存在大量背景健康DNA。我们的建议是开发方法来处理血液样本，降解健康的DNA序列并富集信息丰富的肿瘤DNA，从而易于检测和表征。我们已经开发了一种新方法（SNARE），我们希望根据现有的有前途的富集方法（名称Pro）进行测试。这些方法的广泛使用将需要自动化，我们将在机器人台式和微流体平台中开发自动化。最后，我们将使用来自乳腺癌患者的一组血液样本进行定量评估最佳性能方法，这些方法应该对这些样品中的ctDNA进行更敏感的检测，并且需要较便宜的DNA测序。总而言之，该项目应有助于成功地分析癌症患者的血液样本更便宜，更可靠，从而减少所需的活检手术数量，并实现更多基于证据的癌症治疗。