医学论文
液体活检有望做到癌症的早期发现
2019-05-24 医学论文 

‘Liquid biopsy’ for cancer promises early detection


Ateam of researchers has taken a major step toward one of the hottest goals in cancer research: a blood test that can detect tumors early. Their new test, which examines cancer-related DNA and proteins in the blood, yielded a positive result about 70% of the time across eight common cancer types in more than 1000 patients whose tumors had not yet spread—among the best performances yet for a universal cancer blood test. It also narrowed down the form of cancer, which previously published pancancer blood tests have not. 


The work, reported online today in Science, could one day lead to a tool for routinely screening people and catching tumors before they cause symptoms, when chances are best for a cure. Other  groups, among them startups with more than $1 billion in funding, are already pursuing that prospect. The new result could put the team, led by Nickolas Papadopoulos, Bert Vogelstein, and others at Johns Hopkins University in Baltimore, Maryland, among the front-runners.


“The clever part is to couple DNA with proteins,” says cancer researcher Alberto Bardelli of the University of Turin in Italy, who was not involved in the work. The researchers have already begun a large study

to see whether the test can pick up tumors in seemingly cancer-free women. 


Genetic mutations drive the growth of cancer cells, and dying cells shed some of this mutated DNA into the blood. The Johns Hopkins group and others have shown that so-called liquid biopsies of blood-borne tumor DNA can reveal, for example, whether a patient’s cancer should respond to a specific drug. But detecting the scant DNA released by early stage tumors is still challenging. Companies such as the $1 billion Grail, launched in 2016 by sequencing giant Illumina, are using a big data approach, sequencing hundreds of genes in thousands of cancer patients’ blood in search of a definitive set of DNA markers.


The Johns Hopkins researchers and collaborators found that gains in the detection rate tailed off when they added more genes to their test. They decided to sequence parts of just 16 genes often mutated

in different types of cancer. They then added eight known protein biomarkers characteristic of specific kinds of cancer. This bumped up sensitivity and allowed the team to home in on the tissue type of

the tumor. 


In blood samples from 1005 patients with eight types of tumors that had evidently not yet metastasized, the test detected between 33% and 98% of cases, depending on the tumor type (see graph, below). The sensitivity was 69% or higher for ovarian, liver, stomach, pancreatic, and esophageal cancers—all types that are difficult to detect early.







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