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

目前，为了选择最佳治疗方案，大多数癌症患者需要进行一次令人不快且昂贵的外科手术，从他们的肿瘤中取出组织样本，称为活组织检查。然而，所有人都有少量的DNA在他们的血液中自由循环(这些DNA不在他们的血细胞内)，在癌症患者中，一些循环中的自由DNA来自他们的肿瘤。这种肿瘤DNA不同于它们健康的循环DNA，因为它携带着将这些细胞从健康细胞转化为癌细胞的突变。因此，这种循环中的肿瘤DNA(CtDNA)有可能揭示患者癌症的细节，并显示哪些治疗最有可能成功。研究ctDNA的方法已经发展起来，但都受到ctDNA丰度低和血液样本中存在大量背景健康DNA的限制。我们的建议是开发处理血液样本的方法，降解健康的DNA序列，并通过丰富信息的肿瘤DNA，使其更容易检测和表征。我们已经开发了一种新的方法(SNARE)，我们希望与现有的有希望的富集法(NAME-PRO)进行测试。这些方法的广泛使用使患者受益，将需要他们的自动化，我们将在机器人台式和微流控平台上开发。最后，我们将使用一组乳腺癌患者的血液样本来定量评估执行最好的方法，这些方法应该可以更灵敏地检测这些样本中的ctDNA，并且需要更便宜的DNA测序。总而言之，该项目应该有助于成功分析癌症患者的血液样本，使其更便宜、更可靠，从而减少所需的活检手术次数，并使更多以证据为基础的癌症治疗成为可能。

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.