Unlocking The Marvels of ctDNA
By Salomé Blandón Atía
Okay, by now, I’m assuming you know what cancer is. It is commonly known how challenging this disease is to cure and survive. For instance, one of the main problems is how quickly the disease is diagnosed.
When cancer is diagnosed early, the treatment is significantly more successful in fighting the disease. If it is diagnosed later, the patient’s chances of survival drop.
Most cancer cases are found too late when symptoms are visible during the last stages of cancer. The majority of the types of cancer according to NORC, evaluate 57% of all diagnosed cancers currently do not have a recommended screening test, which makes it impossible for early diagnostics to occur.
What if I tell you that there is a potential solution for this? Imagine a tool that identifies numerous types of cancer with just drops of blood. If this was commercialized, early cancer detection could become the norm, and the survival rates could increase.
You do not have to imagine because it is already here.
The Galleri® Test
The Galleri® Test is a cancer screening test that recognizes fifty types of cancer through an identifiable cancer signal. Using this test, it is possible to identify cancer before symptoms appear, when cancer may be easier to treat. It is crucial to get cancer screenings even if someone feels healthy. This test is part of a new, innovative type of detection known as multi-cancer early detection (MCED), which uses genomic science and machine learning. MCEDs have an 85·2% (95% CI 79·8–89·3) accuracy in predicting the site of the cancer tumour’s origin.
The signal to identify the disease is from the DNA cancer cells or cell-free DNA (cfDNA) found in the bloodstream. Circulating free DNA (cfDNA) is tiny bits of broken DNA released into body fluids like blood, urine, and spinal fluid. These bits have sizes that match particular structures, helping protect the DNA from being broken down by natural processes. In addition, circulating tumour DNA (ctDNA) refers to either single- or double-stranded DNA that tumour cells release into the bloodstream, carrying the mutations present in the original tumour.
cfDNA and ctDNA are two concepts that often get mixed up. The difference is that cfDNA (cell-free DNA) is a broader term encompassing the different types of DNA that flow in the bloodstream, while ctDNA (circulating tumour DNA) is a more specific part of cfDNA.
All body cells release their contents after they die, and cancer cells are no exception. The DNA is released through the death cycle of a cell as they are dropped into the bloodstream. This is what the Galleri® Test identifies and gives a diagnosis by reviewing over one million DNA methylation sites in the blood.
Methylation sites are specific spots on DNA or RNA where a tiny chemical tag called a methyl group is added. A methyl group is a common way genes are regulated. For DNA, this often happens at specific pairs of DNA building blocks called CpG dinucleotides. Changes in this process can be linked to diseases like cancer. Scientists use techniques like bisulphite sequencing to figure out and study these spots on the DNA, helping us understand how genes are controlled.
To find the cancer, methylation sites are analyzed through the DNA methylation patterns, primarily in the genes related to cancer development. Abnormal DNA methylation patterns are a hallmark of many cancers, leading to changes in gene expression that contribute to tumour formation and progression.
In the progression of cancer, millions of genes are either silenced or activated. Although some genes are silenced because of mutations, it is usual to find silenced genes due to altered DNA methylations. These changes help the cancer evolve and show characteristics the disease typically has.
Back to the Galleri® Test, this test provides greater hope and opportunity to identify cancers early. The chances of survival increase if the disease is found in the early stages, and the patient can live for years as long as the cancer is treated and managed.
However, there are some disadvantages. The first one is the price. Because this is a new, innovative technology, it makes sense it is expensive. But most people have no access to these types of luxuries. Therefore, they are unable to utilize the test.
Moreover, the Galleri® Test is not recommended to be used by itself, as diagnostic testing is needed to verify the existence of a tumour. The test is an addition to a patient’s healthcare plan.
As well, the test cannot identify all types of cancer. As a consequence, this creates false positives and false negatives. A false positive occurs when a scientist incorrectly concludes that something is true when, in reality, it is false. In contrast, a false negative occurs when a scientist inaccurately determines that something is false despite it being true.
Fortunately, there is a relatively low positive predictive value and a high negative predictive value. The significance of this lies in the fact that there is a relatively low chance of false positives, or low positive predictive values, and high reliability in ruling out the presence of the condition when the test indicates a negative result, also known as high negative predictive values. These characteristics enhance the test’s accuracy and reliability, contributing to its effectiveness in cancer detection.
The positive predictive value is the percentage of individuals who receive “Cancer Signal Detected” results and are subsequently diagnosed with cancer. In this case, the percentage is 43.1%. For the positive predictive value, 4 out of 10 individuals with a “Cancer Signal Detected” result are expected to have a confirmed cancer diagnosis following a diagnostic workup.
The negative predictive value is known as the percentage of individuals who receive results showing there is “No Cancer Signal Detected” and do not have cancer. This provides confidence to patients, as they can be fully aware that if this result is given, it is most likely accurate. For this case, 98.5% of a negative predictive value occurs.
The Galleri® Test provides people with the possibility of a healthier, longer future. It targets a problem that has been in the cancer area for a long time: early diagnosis.
With early diagnosis of fifty types of cancers, a large area can be covered, and highly accurate results are given. If this test is given to a large population, it would help cancer patients get help faster, enabling an increase in their survival rate.
The test marks the start of a new era of multi-cancer early detection (MCED) since they have created a test that has disrupted its market.
Just with a few drops of blood.
Further Reading
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