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Mary Royal almost skipped her mammogram.

At 51, the mother of four from Wichita Falls, Texas, was busy,

tired, and juggling the overlapping demands of work, family, and everyday life. The appointment felt routine—easy to reschedule and easy to dismiss. In a decision that would change everything, she went.

In 2023, Royal was diagnosed with stage 2B multicentric invasive lobular and ductal carcinoma. What followed was a cascade familiar to many cancer patients but deeply personal in its toll: a double bilateral mastectomy, months of chemotherapy and radiation, and the discovery of a nodule in her chest cavity. Another scan later revealed a mass on her ovary, prompting a preventative radical hysterectomy. By the end of the year, Royal had endured positron emission tomography (PET) scans, injections, fasting, and what she called “all that nuclear medicine.”

For many patients, completing treatment is supposed to signal relief. In reality, it often marks the beginning of a new phase—one defined by uncertainty. Surveillance imaging, blood tests, and follow-up visits can feel like checkpoints in an endless waiting game. Every scan carries both hope and fear.

Royal knows this phase well. Like many survivors, she lives with what patients and clinicians call scan anxiety. “I’ve never met a person diagnosed with cancer who did not live with scan anxiety,” she said.

That anxiety eventually led her to consider a different way of monitoring her disease—one that looks not for tumors large enough to be seen on a scan, but for microscopic traces of cancer that may remain in the body after treatment. These traces are known as measurable, or minimal, residual disease (MRD).

MRD basics

MRD refers to the small number of cancer cells that can persist after treatment, even when imaging and conventional tests show no evidence of disease. These cells are often invisible to computed tomography (CT), magnetic resonance imaging (MRI), or PET scans, yet they can drive relapse months or years later.

Historically, MRD testing has been best established in hematologic malignancies such as leukemia, lymphoma, and multiple myeloma. In these diseases, molecular and flow-based techniques can detect one malignant cell among tens of thousands, or even millions, of normal cells. In solid tumors, however, detecting MRD has been far more challenging. That is now changing.

Advances in liquid biopsy technologies allow researchers to analyze circulating tumor DNA (ctDNA): tiny fragments of DNA shed by cancer cells into the bloodstream. With increasingly sensitive assays, it is now possible to detect residual disease at levels far below what imaging can reveal.

MRD matters because cancer recurrence is often a race against time. The earlier residual disease is detected, the greater the opportunity to intervene—whether by intensifying therapy, switching treatments, or, in some cases, sparing patients from unnecessary additional therapy if no disease is detected.

Regulators are taking note. In January 2026, the U.S. Food and Drug Administration (FDA) issued draft guidance supporting the use of MRD negativity as an endpoint in clinical trials for multiple myeloma. The move signaled growing confidence in MRD as a meaningful surrogate for long-term outcomes, potentially accelerating clinical trials and access to new therapies.

Deciding to look closer

When Royal’s oncologist suggested the Personalis NeXT Personal^® test, a blood-based MRD assay, her initial reaction was hesitation.

“I said, ‘Let me think about it,’” she recalled. As she researched the test online, her anxiety rose. “I thought, ‘No, thank you. I have had so much anxiety already.’”

Her husband disagreed. “You are insane,” he told her, “Why would you not want to do that?” Her oncologist offered a different perspective: “What is the point of science if we don’t use it?”

“That really resonated with me,” Royal said.

She agreed to the test and had her first ctDNA draw in early 2024. Since then, she has taken it 13 times.

“Seeing that zero in the results is a huge relief,” she said. “I really appreciate how much easier the test is on me, both mentally and physically. Now, I cannot believe anyone would say ‘no’ to this. It brings me so much comfort. And I want to know what to do next. I don’t want to just sit around waiting for something when I have the ability to see things early on.”

Her experience reflects a growing shift in survivorship—from episodic imaging to continuous molecular monitoring.

An ultrasensitive approach

For Richard Chen, MD, CMO at Personalis, the goal of ultrasensitive MRD testing has always been to address the uncertainty patients live with after treatment.

“Our NeXT Personal test pioneered ‘ultrasensitive MRD’ down to about one part per million of ctDNA, designed to be a leap forward in detecting very small traces of cancer from a blood sample earlier,” Chen said.

The test is tumor-informed, meaning that it begins with whole-genome sequencing of a patient’s tumor. From that data, up to approximately 1,800 tumor-specific mutations are identified to create a personalized molecular signature. Blood samples are then analyzed for that signature.

“The groundbreaking clinical data that we have published in lung and breast cancer shows that the ultrasensitive capabilities of NeXT Personal enable it to detect cancer many months to years ahead of imaging,” Chen said, “potentially allowing for earlier intervention and treatment of the patient.” Equally important, he added, is the reassurance that a highly sensitive negative result can provide.

Personalis is expanding MRD testing beyond simple detection. A new opt-in feature, the Real-Time Variant Tracker^®, allows clinicians and patients to view potentially actionable mutations detected in ctDNA, including those associated with treatment resistance.

MRD testing is increasingly viewed not just as a prognostic tool, but as a way to actively guide care. Chen outlines three major applications: earlier detection of residual or recurrent disease; earlier de-escalation of therapy for patients who have cleared their cancer at a molecular level; and real-time monitoring of treatment response.

“Cancer is often a race against time,” he said. “If you can detect cancer that’s coming back much earlier than before, then you have the opportunity to intervene earlier with additional treatment for the patient.”

Adding biological precision

Sensitivity alone, however, is not the only challenge in MRD detection. Biological precision—understanding which cells persist and why—is equally important.

Zivjena Vucetic, MD, PhD, CMO at Mission Bio, points to the limitations of bulk sequencing approaches, which average signals across mixed-cell populations.

Mission Bio’s single-cell MRD assay simultaneously detects genetic mutations and surface protein expression across thousands of individual cells in acute myeloid leukemia. This approach reveals whether mutations coexist in the same cell and how they relate to cellular phenotypes.

“Our integrated single-cell approach provides a more biologically precise definition of measurable residual disease,” Vucetic said, which might improve risk stratification beyond conventional molecular or flow-based methods.

By identifying rare, therapy-resistant clones, single-cell MRD technologies offer insight into clonal evolution and emerging resistance. This information can guide treatment selection and drug development.

Decentralizing monitoring

Accessibility and turnaround time are also shaping the MRD landscape. For example, QIAGEN is advancing MRD monitoring by pairing tumor-informed assay design with decentralized digital polymerase chain reaction (dPCR), aiming to make longitudinal molecular monitoring faster, more accessible, and more informative for research and drug development.

In June 2025, QIAGEN announced a partnership with Tracer Biotechnologies to integrate Tracer’s tumor-informed assay design with QIAGEN’s QIAcuity dPCR platform. The approach begins with sequencing a patient’s tumor, often leveraging existing next-generation sequencing (NGS) data, to identify somatic mutations. Tracer then designs personalized multiplex dPCR assays to detect ctDNA carrying those mutations in blood samples.

Running these assays on QIAcuity enables absolute quantification of rare tumor-derived molecules by partitioning samples into thousands of reactions. According to Richard Watts, vice president of partnering for precision diagnostics at QIAGEN, “The result is a decentralized, high-frequency monitoring solution,” with turnaround times measured in hours to days rather than weeks. He noted that this model significantly reduces cost and logistical complexity compared with centralized NGS-based MRD testing while enabling earlier detection of molecular recurrence, often before radiographic changes are visible.

While currently intended for exploratory research use, the platform has clear implications for oncology drug development. By allowing assays to be run on standard dPCR instruments at clinical trial sites, sponsors can avoid centralized sample shipping, simplify global study design, and more rapidly generate data. Frequent sampling also provides detailed insight into tumor kinetics and treatment response, potentially enabling earlier assessments of drug activity.

Looking ahead, QIAGEN anticipates MRD evolving beyond detection toward biological characterization. Emerging single-cell technologies, supported by QIAGEN’s recent acquisition of Parse Biosciences, could reveal why residual disease persists by distinguishing resistant cell populations and non-genetic resistance mechanisms. Watts emphasized that future clinicians will not only ask whether MRD is present, but “why it persists and which pathways sustain it,” signaling a shift toward more precise, biology-driven intervention strategies.

The expanding ecosystem

Beyond ultrasensitive and single-cell approaches, a growing number of companies are contributing complementary technologies that are broadening how MRD is detected, characterized, and monitored across cancer types.

Twist Bioscience, for example, has developed scalable target enrichment solutions for MRD monitoring that support highly personalized approaches to disease surveillance. Its MRD Rapid 500 Panel enables fast design and manufacture of customized capture panels using silicon-based DNA synthesis. By offering panels that range from dozens to hundreds of tumor-specific probes and fast turnaround times, this approach allows researchers to assess adjuvant treatment response at a genomic level while remaining compatible with established NGS library preparation and hybrid capture workflows.

Whole-genome sequencing-based plasma assays are also playing an expanding role in solid tumor MRD detection. Labcorp offers a plasma-based assay for colorectal cancer that uses whole genome sequencing to identify ctDNA associated with MRD. This approach enables the detection of recurrence at a molecular level before clinical symptoms, biological markers, or radiographic evidence emerge, creating an opportunity for earlier and more proactive intervention.

In hematologic malignancies, ultrasensitive liquid biopsy platforms are demonstrating the ability to dramatically shorten the time required to detect residual disease. For instance, Foresight Diagnostics has developed a ctDNA-based MRD platform that achieves exceptionally high sensitivity across multiple cancers. In patients with large B-cell lymphoma, this approach can detect ctDNA immediately after treatment, rather than waiting for months or even years for disease recurrence to become apparent through PET or CT imaging.

Comprehensive NGS-based MRD solutions are also advancing in myeloid malignancies. Thermo Fisher Scientific offers an integrated research-use testing solution that combines highly sensitive DNA and RNA assays on a single sequencing platform. This enables the simultaneous assessment of single-nucleotide variants, insertions and deletions, and gene fusions alongside streamlined informatics and reporting designed to simplify MRD data interpretation in research settings.

Meanwhile, dPCR continues to play a crucial role in MRD monitoring, where absolute quantification and extreme sensitivity are required. Bio-Rad Laboratories has long supported droplet dPCR technologies that are well suited for tracking low-abundance disease markers. These capabilities are particularly valuable in both hematologic malignancies and solid tumors, where MRD signals in blood can be vanishingly small yet clinically meaningful.

Pre-analytical precision

As MRD assays push detection limits ever lower, pre-analytical steps such as sample collection and cell-free DNA (cfDNA) extraction become increasingly important.

As one example, Anagha Kadam, PhD, applications and product development scientist at New England Biolabs (NEB), highlights how the Monarch Mag Cell-free DNA Extraction Kit addresses crucial challenges in liquid-biopsy workflows and MRD research.

This kit is a magnetic bead-based solution designed for the reproducible isolation of circulating cfDNA from biofluids like plasma, urine, and cerebrospinal fluid. “The kit can be used to isolate cfDNA for discovery and detection workflows, including ctDNA profiling, cancer biomarker discovery, and oncology diagnostics research,” Kadam explained. This technology efficiently recovers cfDNA fragments in the typical sizes of 150–300 base pairs, and even as small as 50 base pairs, while remaining compatible with common anticoagulant and preservative collection tubes. According to Kadam, “The silica-coated magnetic beads, combined with optimized buffer chemistry, help ensure maximum binding and recovery of cfDNA in manual or automation formats.”

Sensitivity and reproducibility are especially crucial for MRD applications. “A cfDNA isolation method that is compatible with different sample types, and that faithfully isolates cfDNA, is a key consideration when establishing MRD workflows,” Kadam noted. She added that the kit delivers “reproducible, high-quality cfDNA yields from different biofluid samples, without additional post-extraction cleanups,” enabling consistent fragment profiles while saving time. When integrated with NEB’s sequencing and amplification tools, the kit supports streamlined, end-to-end workflows for generating high-quality data from challenging clinical samples.

From waiting to watching

For Mary Royal, MRD testing has not eliminated uncertainty, but has transformed it.

Instead of waiting passively for scans, she feels engaged in her care. Instead of fearing every appointment, she has access to information that helps her understand what is happening inside her body in near real time.

“I want to know what to do next,” she said. “I don’t want to just sit around waiting for something when I have the ability to see things early on.”

As MRD technologies continue to mature, the desire to replace waiting with knowledge is becoming central to modern oncology. MRD is no longer just a research endpoint or laboratory metric. It is becoming a bridge between science and survivorship, offering patients, clinicians, and researchers a clearer signal in the noise of uncertainty.

And sometimes, that signal is a simple zero—small, powerful, and profoundly reassuring.

 

Mike May, PhD, is a freelance writer and editor with more than 30 years of experience. He earned an MS in biological engineering from the University of Connecticut and a PhD in neurobiology and behavior from Cornell University. He worked as an associate editor at American Scientist, and he is the author of more than 1,000 articles for clients that include GEN, Nature, Science, Scientific American, and many others. In addition, he served as the editorial director of many publications, including several Nature Outlooks and Scientific American Worldview.

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