Charged with 12 counts of fraud and facing 20 years in prison? The trial of Silicon Valley's "female Steve Jobs" is imminent.

In its heyday, Theranos was valued at $9 billion (nearly Rs 60 billion), and Holmes appeared on the cover of Forbes magazine in 2014, with bold statements and a black turtleneck sweater that led the media to dub her "the female Steve Jobs.

But in October 2015, the media exposed Theranos' "blood cancer test" as a fraud. The company had purchased Siemens instruments to perform the test and passed off the results as its own.

In March 2018, Holmes and his company, Theranos, were charged with fraud by the US Securities and Exchange Commission (SEC), facing up to 12 counts of fraud. If convicted, Holmes faces up to 20 years in prison. Prosecutors say she willfully misled patients about testing and inflated the company's performance to investors.

Theranos also folded in 2018. According to the latest news, Holmes's opening statement will be held on September 8, 2021, and the trial is expected to last 13 weeks.

In stark contrast, in January 2016, Grail, the first U.S. company to use epigenetic technology to check for cancer, was founded and was a hit, with Google and Bill Gates both participating in the investment. The person in charge of the enterprise pointed out that Grail can develop the corresponding technology, because there is a clear methodology in academia, epigenetics can be used for tumor screening has been proved by many scientists research and experiments, in the field of biology has been recognized. Holmes's so-called "drop of blood to detect cancer" has never explained its scientific principles clearly, nor has it been recognized by professionals.

"The perception of scientists is not determined by the media and public evaluation, but by academic results. Without academic accumulation, even business geniuses cannot make innovations, which is disrespectful to science." The above business leaders said.

Can blood detect cancer?

In fact, the allegations against the US blood-testing company Theranos and its founder Elizabeth Holmes doesn't mean that blood tests can't detect cancer, but rather that the concept of dripping blood to detect cancer is not scientific enough on its own.

So how does a blood test screen for early cancer?

In layman's terms, the human body is made up of countless cells, all of which release DNA and proteins into the bloodstream, including mutated cancer cells. The mutated DNA and proteins contained in cancer cells can be detected by blood tests when they enter the bloodstream, thus recognizing early-stage cancers.

For example, Fudan University researcher Chen Xingdong's team found that for five common malignant tumors, colorectal, esophageal, liver, lung, and gastric cancers, trace tumor methylation, an early cancer signal, is present in the blood circulation and can be detected non-invasively.

Additionally, the team found that cancer signals are present in the bloodstream early in the development of the disease, even years before symptoms are diagnosed. Using samples from the Taizhou Prospective Cohort, the Fudan research team demonstrated in a rigorous way that DNA methylation sequencing can detect cancer earlier than traditional diagnostic methods.

The Fellowship's researchers designed a machine learning method, PanSeer, based on ctDNA methylation traits, with 94.7% specificity in the training set, and 88% and 91% sensitivity for patient samples collected after diagnosis, and for samples collected before diagnosis, respectively. In an independent test sample set, the team achieved 88% sensitivity on 113 post-diagnosis patient samples while reproducing 96% specificity on 207 healthy control samples. In addition, 95% assay sensitivity was achieved in 98 samples collected 1-4 years prior to diagnosis.

According to Dr. Rui Liu, co-founder and CTO of Kundun Genetics and co-corresponding author of the above study***, the biggest technical breakthrough of this study is the method of constructing plasma free DNA targeted sequencing libraries by using semi-targeted PCR, which dramatically improves the efficiency of the enrichment of methylated targets, and solves the problem of the scarcity of ctDNA in the plasma of patients with early-stage cancers, high loss rate of DNA in the conventional method, and high detection sensitivity of the test. loss rate and limited detection sensitivity in the plasma of early-stage cancer patients.

Chen Xingdong said that some of the current detection methods in foreign countries that are similar to early screening studies for multiple cancers are very costly. This study confirms that simply sampling a small amount of DNA from a single tube of blood can be detected, making it effective and affordable as a potential first-line early cancer screening tool.

It's a liquid biopsy

Cancer detection through blood is a liquid biopsy technique. Liquid biopsy is a diagnostic technique that detects biomarkers and performs tumor analysis by collecting samples of human blood, fluid, urine, saliva and other body fluids. The workflow of liquid biopsy includes sample collection, logistics and transportation, sample testing, and test reports.

Although tissue biopsy is the gold standard for tumor diagnosis and can be used for morphological and molecular assessment, studies have shown that tissue biopsy cannot capture the full genomic profile of a patient's entire tumor load because of heterogeneity within and among tumors in the same patient; in addition, tissue biopsy is more invasive, may not provide enough samples for pathology testing, is not suitable for dynamic monitoring, and some tumor locations are not suitable for puncture. In addition, tissue biopsy is more invasive, may not provide enough samples for pathology, is not suitable for dynamic monitoring, and some tumor locations are not suitable for puncture.

Liquid biopsy has the advantages of being non-invasive and efficient.
Liquid biopsy is a convenient and fast sampling process, less invasive to the human body, and good compliance. It is also simple to perform, less dependent on healthcare resources, and has high accessibility for multiple sampling. The test cycle is usually 1-2 weeks.

However, liquid biopsy also has problems with poor capture ability, low detection rates, and large individualized differences, and its technology is still in the process of further improvement.

According to the analysis of the Head Leopard Institute, there are three main analytes in liquid biopsy technology. The first is the detection of circulating tumor cells (CTCs). These are tumor cells that enter the peripheral blood circulation either spontaneously or as a result of diagnostic and therapeutic manipulation from solid tumor foci. Because they carry a large amount of information related to tumor generation, metastasis, and drug resistance mechanisms, they can be used to monitor the dynamics of tumors and the effects of clinical treatments, as well as to detect drug sensitivity.

Currently, the clinical value of CTC in determining the prognosis of patients with metastatic colorectal cancer, breast cancer, and prostate cancer has been confirmed.

The second is the detection of circulating tumor DNA (ctDNA). ctDNA refers to circulating DNA fragments released by tumor cells into the human blood system, derived from necrotic or apoptotic tumor cells, CTC and tumor cell exosomes, and contains gene mutations specific to the tumor genome. ctDNA can be used to detect small residual foci and occult metastatic foci as well as to monitor the effect of tumor treatment, and can also be used to analyze the genetic information changes of tumor cells such as mutations, amplifications, deletions, etc. ctDNA has been shown to have clinical value in the prognosis of patients with prostate cancer. The ctDNA test can detect tumors before the appearance of clinical symptoms and has the potential to assist in early diagnosis.

The third is exosome detection. Exosomes are vesicles shed by tumor cells, which are distributed in various body fluids such as blood, saliva, and urine. Exosomes are usually produced and released in large quantities and maintain stable vesicle composition under the protection of an external lipid membrane, which carries quantitative information that can predict the presence of a malignant tumor.

Currently, in the liquid biopsy early screening market, startup biotech companies such as Burning Stone Medical and Panspermia have made extensive layouts. Cancer screening startup Grail, recently acquired by US gene sequencing giant Illumina for $8 billion, is also developing liquid biopsy technology in the hope of early screening for cancers such as ovarian cancer.

Huge market potential

It is understood that each year in China, more than 3.5 million new cancer cases, more than 2 million deaths, prevention and control of the situation is grim. In recent years, the incidence of lung cancer, breast cancer and colorectal cancer has shown a significant upward trend, and the incidence of liver cancer, stomach cancer and esophageal cancer remains high.