Updated: Apr 21
ScienceMag.Org March 26, 2021, 2:00 PM |Technology Feature|”Catching cancer extremely early” by Mike May
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Image not from Science. From Molecular Cancer Research April 2020. To provide an overview of the general molecular biology involved in analyzing ctDNA. Methods referred to in the Science article may be different. Abbreviations ctDNA cell free tumor DNA, PCR polymerase chain reaction, NGS next generation sequencing, WGS whole genome sequencing, WES whole exome sequencing. The ScienceMag posting focuses on screening well persons for cancer, something that's controversial, but this figure shows the range of other uses of ctDNA from a simple blood draw.
Image not from Science. From ars.els.cdn.com. Provided to give a simple graphic overview of how Artificial Intelligence (AI) fits into analyzing research data from microscopic sections, imaging-XRAY, CT, MRI and ctDNA or other DNA. AI fueled algorithms are developed after extensive studies, not the least of which is machine learning, and retrospective and prospective clinical trials before the methods are deemed suitable for patient use.
“A variety of tests under development promise easier and more complete cancer-screening capabilities. With just a single blood sample, some diagnostics will search for signs of dozens of cancers. In addition to their biological capabilities, these screening methods benefit from advanced computation, including artificial intelligence. The questions is, how well might these tests work?”
It is well known that catching cancer early is the key to longer post-diagnosis survival. According to David Crosby (Cancer Research UK) “’57% of people with lung cancer survive their disease for 5 years or more when diagnosed [early] at stage 1 compared with only 3% of those diagnosed at [late] stage IV.” A key problem is getting people to seek screening, Sam Cykert (University of North Carolina School of Medicine) comments “’By far, the highest lung-cancer rates in Americans are among black men, and they hardly ever get CT screening.’” But maybe if only a simple blood test were involved more would get screened possibly as part of an annual physician check-up. According to John Ofman (GRAIL),”’Current guideline-recommended screenings…in the United States…cover only five cancers and screen for a single. Cancer at a time.’”
Newer tests of cancer "biomarkers", that may eventually hit the market, will likely be based on analyzing circulating tumor DNA (ctDNA)-pieces of DNA shed into the blood from developing cancer cells. Such ctDNA “might account for just 0.1% [of all DNA]” but once extracted can be analyzed by Next Generation Sequencing (NGS) for modifications associated with cancer. Companies working in this arena include Guardant Health (Colon Cancer), Grail, and others including Thrive (Part of Exact Sciences). Isaac Kinde (Co-Founder of Thrive) is developing a “blood test that analyzes mutations…in ctDNA to screen for multiple cancers.” Kinde cautions that “the sensitivity of any ctDNA-based test” will “vary due to biology”. Some cancers “shed more ctDNA than others.” Early data demonstrate the promise of this new technology. Grail’s “technology [was used] to detect signals in the blood for more than 50 cancers” and in one study, at Intermountain Precision Genomics (Lincoln Nadauld-Oncologist), cancers were found in “patients who were previously asymptomatic.”
Besides leveraging modern molecular biology like NGS, “the enormous amount of data collected in cancer screening” requires high power computation including Artificial Intelligence that has been developed in complex multi-site-international studies. Of course, improvements in early detection and access are just one tool in the battle against cancer. “Changes in behavior must also be encouraged.”
What are the next steps? Lincoln Nadauld comments “’I foresee patients coming in for their well-patient visit, and while they’re getting their cholesterol checked…they will also get a blood test to see if they have one of dozens of different kinds of cancer.” Cykert follows on “’That takes a system-running the tests, training people to explain the tests and the treatment options, and getting that patients treated.”