Multi-cancer early detection from a single blood draw
Multi-cancer early detection (MCED) technology is one of the most promising tools in the war on cancer. Today, many cancers are found too late, when prognosis is often poor and treatment options are limited. Recent advances in next-generation sequencing and machine learning have enabled the development of multi-cancer early detection testing.
In 2021, GRAIL introduced a first-of-its-kind commercially available MCED test, the Galleri® test, which detects a signal shared by many cancers, including many cancers without recommended screening, with a single blood draw. MCED testing allows patients to be screened for a shared signal by more than 50 cancer types, increasing the chance of finding cancer early.1
The Galleri test does not detect a signal for all cancers and not all cancers can be detected in the blood. False positive and false negative results do occur.
How the Galleri multi-cancer early detection test works
The Galleri test sequences DNA fragments circulating in the blood and uses a machine learning algorithm to determine whether those DNA fragments originate from healthy cells or cancerous cells, and if the latter, predicts the tissue type of organ associated with the cancer signal.
Two principles of biology behind the Galleri test: DNA shedding & methylation
DNA shedding is the natural process by which all dying cells in the body, healthy or diseased, shed small amounts of DNA into the bloodstream. Cancerous cells, if present in the body, also release DNA, and so the blood may carry a mixture of DNA fragments from healthy and diseased or cancerous cells. To determine if each DNA fragment in the blood came from a cancerous cell or a healthy cell, methylation comes into play.
Methylation is a natural process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence by signaling which sections of DNA to turn on or off. Typically, methylation turns genes “off” and demethylation turns genes “on.”
Using these two principles, the Galleri test has three scientific steps:
- Extract and sequence the DNA fragments from the blood (assay)
- Determine if DNA fragments may have originated from cancerous cells (machine learning classifier)
- If cancerous DNA fragments are detected above a certain threshold, identify which cells the cancerous fragments came from (cancer signal-of-origin prediction, or CSO).
Benefits of multi-cancer early detection
Treating cancer starts with knowing you have it. The vast majority of cancers show no symptoms until later stages, when treatment options may be limited. The public health goal of commercializing an MCED test is to increase cancer detection rate without increasing the burden on healthcare systems. To do this, GRAIL has developed a test with high specificity that is able to predict CSO while minimizing testing-associated potential risks, including overdiagnosis.
The promise of a better future
Recent research (modeled data) shows that adding annual testing with multi-cancer early detection blood tests to the currently recommended screening tests may shift detection to earlier stages, suggesting that the five-year cancer mortality rate could be reduced by 39% for cancers that can be detected (or an approximate 26 percent reduction in overall cancer related deaths).3
The Galleri test is the first-of-its-kind MCED blood test that can detect a signal shared by more than 50 types of cancer, including more than 45 of which have no recommended screening.1 Using the Galleri test in addition to recommended screenings has the potential to increase the absolute number of cancers detected.
The Galleri test is recommended for use in adults with an elevated risk for cancer, such as those aged 50 or older. The Galleri test does not detect all cancers and should be used in addition to routine cancer screening tests recommended by a healthcare provider. Galleri is intended to detect cancer signals and predict where in the body the cancer signal is located. Use of Galleri is not recommended in individuals who are pregnant, 21 years old or younger, or undergoing active cancer treatment.
Results should be interpreted by a healthcare provider in the context of medical history, clinical signs and symptoms. A test result of “Cancer Signal Not Detected” does not rule out cancer. A test result of “Cancer Signal Detected” requires confirmatory diagnostic evaluation by medically established procedures (e.g. imaging) to confirm cancer.
If cancer is not confirmed with further testing, it could mean that cancer is not present or testing was insufficient to detect cancer, including due to the cancer being located in a different part of the body. False-positive (a cancer signal detected when cancer is not present) and false-negative (a cancer signal not detected when cancer is present) test results do occur. Rx only.
GRAIL’s clinical laboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and accredited by the College of American Pathologists (CAP). The Galleri test was developed, and its performance characteristics were determined by GRAIL. The Galleri test has not been cleared or approved by the U.S. Food and Drug Administration. GRAIL’s clinical laboratory is regulated under CLIA to perform high-complexity testing. The Galleri test is intended for clinical purposes.
References
1. Klein EA, et al. Ann Oncol. 2021;32(9):1167-1177. doi: 10.1016/j.annonc.2021.05.806.
2. Schrag D, et al. Presentation at European Society of Medical Oncology (ESMO) Congress September 9-13, 2022; Paris, France.
3. Hubbell E, et al. Cancer Epidemiol Biomarkers Prev. 2021;30(3):460-468. Doi: 10.1158/1055-9965.EPI-20-1134.
4. Of the total cancers detected each year 29% are those with grade A,B recommended screening available. Surveillance, Epidemiology, and End Results (SEER) Stat Database: Incidence – SEER 18 Regs Research Data, Nov 2017 Sub. Includes persons aged 50+ diagnosed 2006-2015. Data on file GA-2021-0065.
5. Assumes screening is available for all prostate, breast, cervical, and colorectal cancer cases and 43% of lung cancer cases (based on estimated proportion of lung cancers that occur in screen-eligible individuals older than 40 years). Estimated deaths per year in 2022 from American Cancer Society Cancer Facts and Figures 2022. Data on file GA-2021-0065.
6. United States Preventive Services Task Force (USPSTF). Recommendations Grade A,B,C. https://uspreventiveservicestaskforce.org/uspstf/topic_search_results
7. Surveillance, Epidemiology, and End Results (SEER) Stat Database: Incidence – SEER 18 Regs Research Data, Nov 2018 Sub. Includes persons aged 50-79 diagnosed 2006-2015 “Early/Localized” includes invasive localized tumors that have not spread beyond organ of origin, “Late/Metastasized” includes invasive cancers that have metastasized beyond the organ of origin to other parts of the body. Data on file GA-2021-004.