Moving Past Theranos: Who Are the Real Cancer Blood Screening Start-ups?
With Elizabeth Holmes found guilty of fraud, Theranos’ legacy has cast doubt on efforts to create potentially lifesaving cancer blood screens. But a steady march of clinical data, engineering successes, and FDA backing have shown that these technologies can work when done right.
The Theranos Promise
In 2020, there were 137,234 deaths caused by malignant cancers in the UK, and over 80% were caused by cancers with no recommended screening programme.1,2 These cancers tend to be diagnosed at later stages, when a cure is less likely, treatment is less effective, more burdensome, and costly.3
This is what made the Theranos promise so thrilling: Holmes described an ‘Edison machine’ that could fit on a doctors desktop and perform more than 240 accurate diagnostic tests with a single drop of blood.4 These included ovarian, pancreatic and prostate screens, which are currently not part of the NHS cancer screening programme.5,6
However, court testimony has revealed that the Edison machines were only ever able to perform 12 out of 240 tests, turning to commercial diagnostic equipment for the rest. Now, as Holmes awaits a sentence of up to 20 years in prison on four charges of fraud, it seems the Theranos saga is coming to a close. But the dream of performing cancer diagnostics with small volumes of blood is not over.7,8
As we begin week two of Colorectal month this March, it seems fitting to take stock of the cancer blood-screen landscape and learn about the research teams pursuing Holmes’ goal. Can we ever fulfil the Theranos promise?
Why Theranos’ Technology Failed – The Challenges of Single Drop Screening Tests
The concept was certainly intriguing, but even if Theranos had limitless amounts of time and money, experts doubt they ever could have realised it. One issue is that there is an inherent variability to fingerprick samples. One study reported that haemoglobin varied three times as much when compared to venous blood, and white blood cell count varied six times as much. In addition, interstitial fluid and the contents of ruptured cells also make it into the sample, and you get slightly different amounts of each every time. Finally, there simply would not be enough blood to perform each test.9 Most tests are performed only on the plasma, and some require chemical reactions that alter the blood enough that it can’t be used for other tests, while others extract individual components of the blood, similarly rendering it useless for subsequent tests.4,8
Out From Theranos’ Shadow: What Cancer Blood Tests Are on the Horizon?
GalleriTM – A Multi-Cancer Blood Test
The GalleriTM test is a revolutionary new blood test that detects DNA markers of more than 50 types of cancer in peripheral blood before symptoms appear.10,11,12 In the last decade, scientists have discovered that when cancer cells die, which happens constantly as a tumour develops and grows, they release tiny fragments of DNA into the blood called circulating tumour DNA (ctDNA). This ctDNA carries a footprint of the cancer itself, but the catch is that it is released by both tumour cells and healthy cells alike. The GalleriTM test builds on numerous advances in genetic sequencing technology and artificial intelligence to detect these ctDNA fragments in a blood sample. By scanning for patterns of chemical changes such as DNA methylation, the test, known as a liquid biopsy, identifies ctDNA fragments that are unique to cancer cells, and not found in healthy cells.13
In September 2021, results from the Circulating Cell-free Genome Atlas study, a clinical validation study of 15,254 participants (8584 with cancer; 6670 without cancer), revealed that the GalleriTM test can successfully identify 51.5% of cancers across all types and all stages. Because the amount of tumour-derived ctDNA tends to increase as a cancer becomes more advanced, the test was better at detecting later stage disease: from 16.8% at the earliest stage I, 40.4% at stage II, 77% at stage III and up to 90.1% at stage IV. Notably, the GalleriTM test was also able to identify the tumors’ organ sites a staggering 88.7% of the time, potentially giving clinicians a head-start in targeting the disease for treatment.13
Now we know the GalleriTM test works, the NHS aims to test it in the real world, where we don’t know which patients have cancer, to see if the test can detect these cancers sufficiently early and accurately to make a difference to people’s lives. The NHS-Galleri trial is a randomised controlled trial that aims to enroll 140,000 volunteers from different backgrounds and ethnicities aged between 50 and 77. Initial results of the study are expected by 2023. If successful, the NHS in England plans to extend the rollout to a further one million people in 2024 and 2025, where it could play a major part in achieving the NHS Long Term Plan to catch three quarters of all cancers at an early stage.10
Guardant Health and Foundation Medicine – Comprehensive Cancer Genomic Profiling in Blood
In August 2020, the FDA gave their first stamp of approval to two liquid biopsy tests, FoundationOne Liquid CDx by Foundation Medicine and Guardant360 CDx by Guardant Health. While the FDA has approved other blood tests that check for the presence of a single gene mutation in tumour DNA, these are the first approved tests that check for multiple cancer-related genetic changes.14,15,16
Both tests work in a similar way to GalleriTM. From a single blood draw, they identify genetic changes, including mutations, in ctDNA that tumours have shed into the bloodstream. Guardant360 CDx detects changes in more than 60 different genes. FoundationOne Liquid CDx, meanwhile, targets 324 genes in ctDNA. Doctors can then use that information to determine if there is a targeted therapy or immunotherapy that is likely to work for the patient.14 As such, FoundationOne Liquid CDx was approved as a companion diagnostic for three lung cancer therapies and a prostate cancer therapy. Guardant360 CDx was approved as a companion diagnostic for osimertinib (Tagrisso), a lung cancer therapy.14,15,16 Clinical studies to support additional companion diagnostic labels for both tests are ongoing.17
Conclusion
With ctDNA blood tests, we are taking tangible strides towards the possibility of detecting and treating cancer before symptoms develop, and giving people the best possible chance of beating the disease. But there is still a long way to go, early stage cancer detection rates need to be improved and these technologies are yet to prove themselves worthy in the real world. However, in answer to the question, can we ever fulfil the Theranos promise for routine cancer screening? My answer is an optimistic yes, and we are much closer now than a decade ago. What do you think?
By James Cranston
