报告题目：LIQUIDBIOPSY: PROMISES AND CURRENT CHALLENGES
报 告 人：NikolaySergeev, PhD.
邀 请 人：李庆阁教授
Abstract: Liquid biopsy is a non-invasive alternative to surgical biopsies with a great promise in cancer diagnostics, therapy selection and monitoring. Different liquid biopsy tests target different biomarkers, such as cfDNA (ctDNA), RNA (mRNA, miRNA, lncRNA), proteins, exosomes and circulating tumor cells (CTCs) in various bodily fluids including blood, urine and saliva. A variety of well-developed molecular methods such as: NGS, qPCR, ddPCR, Sanger sequencing, microarrays, bead arrays and others can be used to interrogate various biomarkers with high sensitivity and specificity. Recently, in 2016, the FDA approved the first liquid biopsy test for detecting EGFR alterations to aid physicians in identifying patients who may benefit from a targeted therapy. This new test enables access to precision medicine for patients, which are too ill or are otherwise unable to provide a tumor specimen for genetic testing, and thus benefit from a better available treatment.
Serial ctDNA measurements are currently being used to monitor responses to therapies and to detect tumor relapses as well as emerging drug resistance during treatment. As the first step, a comprehensive profiling of the specific somatic alterations in tumor is performed by using NGS in order to identify the presence of drugable targets and create tumor’s “fingerprint”. Regular measurement of these mutations in ctDNA using NGS or less expensive molecular techniques during the course of treatment can complement or even replace the repeated invasive biopsy, which may be required for monitoring therapy success. Additionally, one the main promises of liquid biopsy is to detect tumor relapse much sooner than it can be done using imaging techniques.
However, there is still a substantial gap between liquid biopsy as a research approach and a clinical tool. Several main factors including: biological variability, sample quality, tumor type and heterogeneity, selected targets, sensitivity/specificity of used methodologies, cost, data analysis and interpretation play a key role in defining the practical utility and adoption of liquid biopsy tests. Using an example of ctDNA analysis from blood, we present an overview of major challenges, which hinder a wide adoption of liquid biopsy tests in clinical practice. Several strategies to improve the sensitivity, specificity and clinical utility of liquid biopsy assays will be discussed.