The protagonist of the "blood test for cancer" scam was convicted!

▎Editor of WuXi AppTec's content team On January 3, local time, the verdict of Elizabeth Holmes, the founder of Theranos, was announced
.

The entrepreneur who was once famous for his “blood test for cancer” was found guilty of four criminal fraud charges.
Unless the verdict is overturned on appeal, Holmes will face jail
.

Holmes' entrepreneurial story began in 2003, when she dropped out of Stanford University at the age of 19 and founded Theranos, a blood testing company
.

After several years of development, the company's equipment claims to be able to detect hundreds of indicators with just a few drops of blood, and screen out a variety of diseases including cancer and diabetes
.

This "revolutionary breakthrough" made Theranos and Holmes rise to fame
.

In 2015, Theranos company's peak valuation reached 9 billion U.
S.
dollars, and Holmes was also included in Forbes's list of the richest self-made women in the United States
.

However, the bubble burst only in a moment
.

In October 2015, a report in The Wall Street Journal exposed a series of deceptive practices by Theranos, pointing out that the blood test results of the "new equipment" were actually mostly done by traditional equipment
.

With the results of the half-year survey released, Holmes turned from a star entrepreneur to a business liar overnight
.

What followed was the collapse of Theranos and Holmes' subsequent prison life
.

Elizabeth Holmes (picture source: https:// domain) Holmes's "blood test for cancer" has long been recognized as a scam that people spurned, but for scientists, cancer is the liquid Biopsy, or blood test, is indeed an emerging field that has attracted much attention, and progress is endless
.

So, what is the current development of liquid biopsy for cancer? How far are we from the "blood test for cancer"? In the early stage of cancer, patients often lack obvious characteristic symptoms, and the cancer often has metastasized when it is discovered
.

This is also an important reason for the high mortality rate of various cancers
.

Therefore, achieving early screening is the key to improving the survival rate of cancer patients
.

In liquid biopsy, the most common detection target is circulating cell-free DNA (cfDNA)
.

cfDNA is DNA fragments that are free in plasma.
These fragments with a length of only about 150 base pairs usually come from normal tissues, but for cancer patients, cancer cells in their bodies also contribute a small portion of cfDNA
.

These DNA fragments containing mutations related to cancer have become the main detection targets for liquid biopsy
.

However, the development of detection tools based on liquid biopsy is not smooth
.

On the one hand, early-stage cancer patients release low levels of DNA fragments into the plasma.
In extreme cases, less than 0.
1% of cfDNA comes from cancer cells.
It is not easy to detect the DNA fragments of cancer cells
.

Another problem is the existence of false positives: in addition to cancer, the benign proliferation of blood cells may also produce mutations, and this "unexplained clonal hematopoiesis" may also be mistaken for cancer signals
.

In addition, because cancers in different locations may produce similar signals, it is difficult to identify the source of cancer cells
.

Image source: 123RF Faced with such a situation, in recent years, some studies have begun to try new strategies
.

One of them is the detection of the introduction of protein markers
.

In 2018, the Johns Hopkins University research team published a revolutionary "Science" paper
.

This research combines cfDNA sequencing and cancer-related serum protein markers to develop an algorithm for screening cancer and identifying the source of cancer tissue
.

Through the detection of 16 genes and 8 proteins, this algorithm called CancerSEEK can detect 8 different types of cancer
.

In the test of thousands of cancer patients, the average detection rate of CancerSEEK is 70%, and the detection rate of ovarian cancer and liver cancer is as high as 98%
.

The test of blood samples from healthy volunteers showed that the specificity of the test exceeded 99%, which effectively avoided false positives
.

Two years later, CancerSEEK went further
.

In another prospective study published in Science, CancerSEEK's test subjects were replaced with nearly 10,000 healthy women who had no symptoms to simulate real-world conditions
.

As a result, CancerSEEK detected a total of 26 cancer patients that were not detected by traditional methods
.

These cancer cases include 10 types, of which 7 (such as ovarian cancer, kidney cancer) lack approved traditional screening methods
.

▲The working principle of CancerSEEK algorithm (picture source: reference [4]) On the other hand, traditional screening methods additionally screened 22 cancer patients
.

Therefore, combining CancerSEEK with traditional screening methods can double the number of cancer cases screened
.

This study also showed a low false positive rate
.

A total of 101 false positives were detected using CancerSEEK alone, with a false positive rate of about 1%; after combining with PET-CT, the false positive rate dropped to less than 0.
4%
.

Another liquid biopsy strategy is to detect DNA methylation signatures
.

For cancer patients, the number of DNA methylation changes is numerous and the distribution of sites is abundant.
This feature can improve the sensitivity of liquid biopsy
.

The methylation characteristics of different tissues are different during the development process.
Therefore, the detection of methylation characteristics to determine the tissue source of DNA should also have sufficient specificity
.

In 2020, a study published in the Annals of Oncology conducted a trial of 15,000 people and found that the overall detection rate of this method for early and mid-stage cancer was 44%, and the specificity of the detection reached 99.
3%, and it could be judged 93% of the known cancer sites
.

So, how far are these breakthroughs from really being used by us? In fact, both the CancerSEEK developed by Thrive Early Detection and the DNA methylation test results of GRAIL have obtained the FDA-approved breakthrough medical device designation, and more large-scale trials are in progress
.

In addition, we can also see that other companies and research institutions are trying to achieve liquid biopsy of cancer through their own methods
.

It may be several years before these testing tools are finally approved for the market, but there are still some clinical trials and several years, but only by being down-to-earth and speaking with data can a truly reliable screening tool be created, rather than the next Holmes
.

Reference: [1] Joshua D.
Cohen et al.
Detection and localization of surgically resectable cancers with a multi-analyte blood test.
Science (2018).
https:// .
aar3247[2] Anne Marie Lennon et al.
Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention.
Science (2020).
https:// .
aar3247[3] MC Liu et al.
Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA.
Annuals of Oncology (2020).
https:// (20)36058-0/fulltext[4] Mark Kalinich et al.
Cancer detection: Seeking signals in blood.
Science (2018).
https://