
Liquid Biopsy Consortium
Developing Liquid Biopsy Technologies for Early Stage Cancer Detection

Research
In the era of personalized medicine, it is desirable to have noninvasive or minimally invasive methods to determine and follow longitudinally the molecular composition and characterization of a patient’s tumor, which will help gain a broader understanding of the disease. One such approach is through liquid biopsy that can be used to molecularly characterize the tumor and monitor genetic changes over time using repeat sampling of biofluids. Liquid biopsy generally refers to detecting circulating tumor cells (CTC), circulating tumor DNA (ctDNA), circulating exosomes and other analytes in body fluids, such as serum, plasma, urine, etc.​​​ The NCI’s Division of Cancer Prevention has developed and sponsored an Academic/Industrial Partnership program designed to advance and validate Liquid Biopsy technologies specifically targeted for early stage cancer detection. Liquid biopsy uses body fluids such as blood, urine, saliva, stool, and sputum from patients suspected to have early stage cancer as well as those at high risk of developing cancer. The Liquid Biopsy Consortium is also working on methods to distinguish cancer from benign disease; or aggressive from indolent cancers. Projects focus on the development of new tools/methods/assays and/or validations of existing technologies/methods involving the capture of DNA, RNA, or exosomes in circulating body fluids.​
Latest Publications
Amplifying Mutational Profiling of Extracellular Vesicle mRNA with SCOPE
Song J, Cho MH, Cho H, Song Y, Lee SW, Nam HC, Yoon TH, Shin JC, Hong JS, Kim Y, Ekanayake E, Jeon J, You DG, Im SG, Choi GS, Park JS, Carter BC, Balaj L, Seo AN, Miller MA, Park SY, Kang T, Castro CM, Lee H. Amplifying mutational profiling of extracellular vesicle mRNA with SCOPE. Nat Biotechnol. 2024 Oct 7. doi: 10.1038/s41587-024-02426-6. Epub ahead of print. PMID: 39375445.
Abstract
Sequencing of messenger RNA (mRNA) found in extracellular vesicles (EVs) in liquid biopsies can provide clinical information such as somatic mutations, resistance profiles and tumor recurrence. Despite this, EV mRNA remains underused due to its low abundance in liquid biopsies, and large sample volumes or specialized techniques for analysis are required. Here we introduce Self-amplified and CRISPR-aided Operation to Profile EVs (SCOPE), a platform for EV mRNA detection. SCOPE leverages CRISPR-mediated recognition of target RNA using Cas13 to initiate replication and signal amplification, achieving a sub-attomolar detection limit while maintaining single-nucleotide resolution. As a proof of concept, we designed probes for key mutations in KRAS, BRAF, EGFR and IDH1 genes, optimized protocols for single-pot assays and implemented an automated device for multi-sample detection. We validated SCOPE's ability to detect early-stage lung cancer in animal models, monitored tumor mutational burden in patients with colorectal cancer and stratified patients with glioblastoma. SCOPE can expedite readouts, augmenting the clinical use of EVs in precision oncology.
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© 2024. The Author(s), under exclusive license to Springer Nature America, Inc.

