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Since many cancers don’t have symptoms early on, they may go unnoticed until they are at an advanced stage. But that is changing, thanks to a newer, non-invasive tool.

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Sources:
https://www.who.int/activities/promoting-cancer-early-diagnosis
https://www.cancer.org/treatment/understanding-your-diagnosis/tests/imaging-radiology-tests-for-cancer.html
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6606043/
https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis#biopsy
https://www.mayoclinic.org/diseases-conditions/colon-cancer/symptoms-causes/syc-20353669
https://www.thermofisher.com/blog/behindthebench/what-is-cell-free-dna-cfdna-seq-it-out-19/
https://onlinelibrary.wiley.com/doi/epdf/10.1111/brv.12413
https://www.frontiersin.org/articles/10.3389/fimmu.2019.00502/full
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196304/
https://mcr.aacrjournals.org/content/14/10/898
https://cebp.aacrjournals.org/content/3/1/67.full-text.pdf
https://pubmed.ncbi.nlm.nih.gov/9274585/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5898924/
https://www.nejm.org/doi/10.1056/NEJMe1401129
https://bmcpregnancychildbirth.biomedcentral.com/articles/10.1186/s12884-019-2518-x
https://www.rbmojournal.com/article/S1472-6483(13)00466-5/fulltext
https://www.mayocliniclabs.com/test-catalog/Clinical+and+Interpretive/113145
https://jamanetwork.com/journals/jamaoncology/fullarticle/2318964
https://www.frontiersin.org/articles/10.3389/fcell.2021.639233/full
https://www.nature.com/articles/s41467-021-22463-y

Images:
https://www.shutterstock.com/image-photo/pet-ct-scan-human-brain-positron-1281190273
https://www.shutterstock.com/image-illustration/cell-free-dna-circulates-freely-blood-1251866005
https://www.shutterstock.com/image-illustration/blue-dna-structure-isolated-on-background-1786268912
https://www.shutterstock.com/image-illustration/illustration-showing-tumor-cell-free-dna-1695908125
https://www.shutterstock.com/image-vector/noninvasive-prenatal-testing-nipt-screening-genetic-1529573861
https://www.istockphoto.com/photo/3d-illustration-of-x-chromosomes-gm143921774-18531432
https://www.istockphoto.com/photo/dividing-breast-cancer-cell-gm477576278-66735807
https://www.frontiersin.org/articles/10.3389/fcell.2021.639233/full
https://commons.wikimedia.org/wiki/File:CtDNA_in_circulation.png
Thanks to Brilliant for supporting  this episode of SciShow.

Go to Brilliant.org/SciShow to learn how you can take your STEM skills to the next level! [♪ INTRO]. For most cancers, the earlier they are  detected, the better the prognosis.

But seeing something deep inside  the body isn’t straightforward. Most of our methods for  finding and diagnosing cancer involve a combination of  imaging and invasive tests. And since many cancers don’t  have symptoms early on, they may go unnoticed until  they are at an advanced stage.

But that is changing, thanks  to a newer, non-invasive tool. It’s basically a blood test for cancer. And some major progress in developing  this tool wasn’t related to cancer, but to genetic testing of fetuses.

The key to this new test lies  in what is called cell-free DNA, which is free-floating DNA in blood plasma,  rather than encapsulated within cells. Now there are some other  blood tests being developed, but we’re going to focus on this one. Cell-free DNA is thought to come mainly  from dying cells throughout the body, and can be found in healthy people  as a result of normal processes.

Though it’s also associated with disease,  such as its original discovery in 1948, when French scientists found  it in patients with lupus. Over the next few decades, scientists  observed that people with certain diseases, including some autoimmune disorders,  cancers, and infectious diseases, have abnormal levels of cell-free DNA. Like, in 1977, researchers looked at 173  cancer patients and 55 healthy controls and found that the levels of cell-free  DNA were significantly higher in about half of those with cancer.

Of that 50%, the levels were even higher  in those whose cancer had metastasized. In the 90s, advances in DNA sequencing helped kick the understanding of cell-free  DNA up a few notches. For instance, in 1994, two groups of  researchers found that pieces of cell-free DNA in cancer patients actually  have the same genetic mutations that tumor cells were known to have.

These studies, and others that followed,  suggested that cell-free DNA held the promise not only to detect cancer, but to pinpoint the type of cancer and  whether treatment is working. But before that promise could be  fulfilled, around the same time, researchers were also developing  ways to learn about fetuses from cell-free DNA in the pregnant parent’s blood. In 1989, researchers found that fetal cells  are present in the parental bloodstream.

A few years later, the same group  hypothesized that maybe cell-free DNA from fetal tissue would be  detectable during pregnancy. In a 1997 paper in The Lancet,  they looked for the presence of DNA from the Y chromosome in  blood samples from the parent. Now most people who bear children  don’t have a Y chromosome.

So detecting it in the bloodstream  would mean that it came from the fetus. The researchers’ hunch panned out,  and they found pieces of Y chromosome in most of those pregnant with  fetuses who had Y chromosomes. That confirmation that cell-free  fetal DNA is a thing that shows up in pregnant people’s blood birthed  a new era of prenatal diagnostics.

Eventually, scientists gleaned that,  out of all of the cell-free DNA in a healthy person’s bloodstream, during pregnancy, about 3 to 15% of it comes from the fetus. What’s more, since parent and fetus  will both typically have 46 chromosomes, any extras would clearly stick out. Extra copies of chromosomes, called  aneuploidies, are often fatal to the fetus.

In other cases, they can cause conditions  that some parents want to prepare for. Like Down syndrome, in which people  have a third copy of chromosome 21. By 2011, tests for conditions in which people have a third copy of some chromosomes  became available to parents.

So far, these non-invasive  prenatal tests, or NIPTs, are used for screening, not actual diagnosis. The results still need to  be confirmed by other tests. But they are highly accurate, in that  they detect over 90% of fetal trisomies.

They also have fewer false positives  than older screening tests, meaning they’re less likely to give  a positive result where none exists. As doctors increasingly started using  NIPTs, one false positive that did happen helped researchers make the cancer connection. A 2013 case study described a  37-year-old pregnant patient.

Extra genetic material from chromosomes  13 and 18 suggested fetal trisomies. But further testing confirmed the fetus  had the typical number of chromosomes. When the patient complained  of pelvic pain after delivery, a fracture in the pubic bone led  doctors to find vaginal cancer.

Because here’s the thing:  aneuploidies don’t just show up at the beginning of life, but  can develop in cancer too. That led to the question:  could an NIPT predict cancer before someone feels symptoms? In a study published in 2015, researchers  obtained consent to administer cell-free DNA tests to thousands of  pregnant patients undergoing routine NIPT.

Their test looked not only at  chromosomes common in fetal aneuploidies like 13 and 21, but at DNA fragments  from throughout the genome. Of four thousand samples, they found  abnormal results in three patients and ended up using further  tests to diagnose cancer, before the patients were aware of any symptoms. These studies and others like them  offered tangible evidence to suggest that cell-free DNA testing could be a powerful,  non-invasive predictor of cancer, and not just in pregnant folks.

It could also be used in  the non-pregnant population, which is most of us, and to  monitor for cancer recurrence. There are still some hurdles  to clear before cell-free DNA is really ready for the big time. One of the biggest will be to  really hone in on separating out free-floating DNA from  everything else in the blood.

Another is to learn more about other conditions that increase the levels of cell-free DNA. The hope is that eventually, doctors will  even be able to use blood tests to suss out which therapies will be most effective  for an individual’s unique cancer. Getting information from someone’s  blood is a huge step up from having to take tissue from harder-to-reach body parts, and from the expensive hassle of imaging.

So all in all, cell-free DNA  is a big win against cancer. Scientists today are still  designing elegant experiments to unlock the secrets of the universe. And you can get a taste of how with  Brilliant’s course Scientific Thinking.

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So thank you for your support! [♪ OUTRO].