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

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.