How GRAIL’s Galleri Test Detects Over 50 Types of Cancer Early

Cancer screening has long been the domain of highly targeted tests, each meticulously designed to identify a specific type of cancer under stringent conditions. Let's explore the Galleri test, a marvel of modern science that rewrites that approach, aiming instead to detect over 50 types of cancer from a single blood sample. Its promise? To catch cancer when it is still curable, through surgery, when interventions can save lives and reshape prognoses.

Test Technique Discovery

The origins of GRAIL's Galleri test read like the opening lines of an extraordinary tale, with a surprise discovery in a very different branch of medicine. In 2015, while scientists at Illumina were refining non-invasive prenatal testing (NIPT)—a method designed to assess the health of unborn children through the mother’s blood—something unexpected surfaced. They found unusual genomic abnormalities in a subset of mothers. Initially, these anomalies seemed irrelevant to the primary goal of fetal health assessment. But as patterns emerged, the researchers realized these weren’t random glitches. Instead, they were detecting cancer signals—faint, fragmented clues from cell-free DNA (cfDNA) circulating in the mothers' blood.

This accidental discovery planted the seed for what would become a revolutionary discovery. The concept of a blood test capable of identifying cancer at its earliest stages, across multiple types, moved from improbable to plausible. GRAIL was spun off as a separate entity in 2016 to pursue this vision, its mission encapsulated in its name. If the test succeeded, it could be nothing less than the “Holy Grail” of cancer detection—a single diagnostic tool that might shift the balance in humanity’s battle against this disease.

Building the Galleri Test: A Monument to Collaboration

Realizing such an ambitious goal was not simple, and required an experienced team across a broad range of expertise. It required a confluence of disciplines, drawing together the brightest minds in genomics, oncology, data science, and bioinformatics. GRAIL launched a series of rigorous studies to refine and validate the test, harnessing the power of large-scale clinical trials and cutting-edge machine learning algorithms.

The Circulating Cell-free Genome Atlas (CCGA) Study, announced in December 2016, served as the test’s cornerstone. Researchers sought to answer two critical questions: Could methylation patterns in cfDNA accurately distinguish cancer from non-cancer? And could those patterns identify the cancer’s location within the body? This foundational research involved sequencing the genomes of thousands of participants, both with and without cancer, to build a library of methylation profiles—unique markers that indicate changes in DNA activity linked to cancer.

Subsequent trials, like the STRIVE Study (2018), expanded the scope. STRIVE enrolled 100,000 women, delving deeper into the test’s ability to predict invasive cancers and ensuring its utility extended beyond theoretical potential. The SUMMIT Study, meanwhile, shifted focus to men and women without elevated cancer risk, aiming to evaluate how well the test could screen a general population for early signs of disease.

By 2020, GRAIL was ready to take the test out of purely observational studies and into clinical settings. The PATHFINDER Study represented this next phase, evaluating the practical implementation of the Galleri test among healthcare providers.

And then there was the NHS-Galleri Trial, a large collaboration with England’s National Health Service. Recruiting 140,000 participants aged 50 to 77, this trial marks one of the most ambitious efforts yet to determine the test’s effectiveness in a real-world population screening context.

Decoding the Process

To understand the Galleri test is to appreciate the convergence of genomics and artificial intelligence. The process is as elegant as it is revolutionary:

1. Blood Collection: A simple blood draw marks the beginning.
2. DNA Analysis: From this sample, cell-free DNA (cfDNA) fragments—tiny whispers of genetic material circulating in the bloodstream—are extracted and sequenced.
3. Methylation Patterns: The test hones in on methylation, a chemical modification that influences DNA activity without altering its sequence. Patterns here can act as red flags, signaling the presence of cancer.
4. Algorithmic Precision: Machine learning algorithms analyze these patterns, assessing whether the DNA suggests a cancerous origin.
5. Locating Cancer’s Source: If a signal is detected, the test uses further pattern recognition to predict the cancer's origin within the body.

Features that Distinguish the Galleri Test

The Galleri test doesn't simply promise detection, it also promises nuanced insights.

• Diverse Detection: It identifies signals from over 50 types of cancer, spanning some of the most elusive and aggressive forms. These are most commonly the types of cancer that can and usually do result in death.
• Accuracy in Origins: For positive results, the test predicts cancer's location with a great deal of precision. Studies have highlighted accuracy exceeding 90% for certain cancers like prostate cancer.
• Early Intervention Potential: While not perfect, its ability to detect cancers at earlier stages opens doors for treatments to work when they are most effective.

Studies and Clinical Realities

The test has been rigorously scrutinized through pivotal studies like the CCGA (Circulating Cell-free Genome Atlas) and PATHFINDER. These efforts underscore its potential while laying bare its challenges.

• Aggressive Cancers: The test demonstrated an aptitude for identifying aggressive forms, potentially prioritizing interventions where they’re most needed.
• Sensitivity and Specificity: While its specificity—at over 99%—minimizes false positives, early-stage sensitivity, around 27.5%, highlights the hurdles of capturing fledgling cancers.
• Prostate Cancer Insights: Among the cancers detected, most were of intermediate or high grade, reinforcing its potential to identify clinically significant cases.

Who Benefits?

The Galleri test is not a universal cancer screening tool. Its design is purposefully tailored to address specific gaps in current diagnostic practices, making it a powerful but selective option for early detection. Let’s unpack the nuances of who stands to benefit most from this innovative blood test and the context in which it is best applied.

The Target Population: Adults Aged 50 or Older

Cancer risk increases with age, a fact that underscores the test’s primary target demographic—adults aged 50 or older. This age group experiences a rise in cancer incidence due to the cumulative effect of cellular changes, genetic mutations, and environmental exposures. For these individuals, the Galleri test offers an additional layer of vigilance, potentially catching cancers that may not yet present symptoms or fall outside the scope of routine screenings.

Within this group, there are further distinctions:

• High-Risk Individuals: People with a family history of cancer or inherited genetic mutations (e.g., BRCA1 or BRCA2) stand to gain the most. For these individuals, the test could serve as a regular monitoring tool, complementing traditional screenings to improve early detection rates.
• Cancer Survivors: Those who have undergone treatment for cancer remain at risk for recurrences or secondary cancers. The Galleri test offers an ongoing method to monitor for new signals of malignancy, giving survivors and their providers a proactive edge.
• People with Known Risk Factors: Smoking, obesity, and occupational hazards like exposure to carcinogens increase the likelihood of developing cancer. For these individuals, the test provides a broad-spectrum safety net that may reveal hidden threats.

Bridging Screening Gaps

While traditional screenings like mammograms, colonoscopies, and Pap smears are effective for specific cancers, they leave substantial gaps. Many of the deadliest cancers—such as pancreatic, ovarian, and esophageal—lack established screening methods for asymptomatic individuals. This is where the Galleri test truly shines:

• Detecting Rare and Aggressive Cancers: Cancers without standard screenings often present symptoms only in advanced stages, when treatment options are limited. The Galleri test can identify these malignancies early, potentially saving lives and expanding treatment options.
• Addressing Multiple Cancers at Once: Current screening methods are siloed, focusing on one cancer type per test. The Galleri test’s ability to detect signals from over 50 types of cancer simultaneously marks a paradigm shift, offering a single test that could identify multiple threats.

Complementary, Not Replacement

Despite its wide scope, the Galleri test is not a substitute for routine cancer screenings. Mammograms, colonoscopies, and other established methods have decades of evidence supporting their effectiveness for detecting certain cancers early. For example, colonoscopies not only detect colorectal cancer but can also prevent it by removing precancerous polyps.

The Galleri test supplements these methods by casting a wider net, particularly for cancers that routine screenings don’t target. Its role is additive—enhancing, not replacing, the existing arsenal of diagnostic tools. This complementary approach ensures that patients receive a comprehensive evaluation, balancing specificity and breadth.

Challenges in Implementation

With great promise come necessary caveats:

• False Positives and Negatives: While rare, they remain a possibility, underscoring the importance of confirmatory testing.
• Detection Gaps: Not all cancers leave detectable traces in the blood, meaning a “no signal” result isn’t definitive.
• Early-Stage Sensitivity: The challenge of detecting cancers in their infancy—a critical goal for any screening tool—remains an area for refinement.

A Glimpse Into the Future

The promise of the Galleri test extends far beyond individual cases. Its widespread adoption could transform how healthcare systems approach cancer screening. Instead of focusing on specific cancers one at a time—breast, cervical, colorectal, for example—this test offers a panoramic view.

The ongoing NHS-Galleri trial is a litmus test for this broader vision. If successful, it could pave the way for national screening programs, where multi-cancer early detection becomes a standard offering. It also opens the door to rethinking healthcare costs, as early detection often translates to less invasive and less expensive treatments.

GRAIL continues to innovate. Its researchers are refining the test to improve sensitivity for early-stage cancers and exploring new ways to apply methylation data. They’ve also committed to funding independent research proposals, creating a global dialogue about the future of cancer diagnostics.