Abstract
About this talk
Minimal residual disease (MRD) can persist in cancer patients even after potential cure, resulting in cancer recurrence and contributing to the low five-year survival rate of cancer patients. Currently, circulating tumor DNA (ctDNA) is the preferred biomarker for MRD detection. However, due to the extremely similar nucleic acid sequences, wild type nucleic acid existing in body fluids in large quantities poses a big challenge to the highly sensitive detection of ctDNA.
We developed a new ultra-sensitive ctDNA detection method using programmable nuclease and dubbed it PASEA (Programmable Enzyme-Assisted Selective Exponential Amplification), which, in the process of nucleic acid amplification, wildtype nucleic acid was specifically cleaved by programmable endonuclease, including Argonaute and CRISPR-Cas systems, to achieve the specific exponential enrichment of ctDNA, so that the detection sensitivity could be lower than 0.01% MAF. We conducted a clinical evaluation of PASEA for tumor efficacy monitoring and MRD detection through follow-up monitoring of patients who received chemotherapy and surgery. Our analysis revealed that PASEA is a powerful tool for predicting cancer recurrence and guiding personalized treatment, offering significant clinical benefits. We also observed that the detection rate of ctDNA in pancreatic cancer was closely linked to treatment status, efficacy and metastatic site.
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