Kevin Donnelly, Chief Executive OfficerMetastatic disease accounts for approximately 90 percent of cancer-related deaths. Although clinicians have access to surgery, ablation, radiation and systemic therapies, determining which patients are most likely to experience durable outcomes following local intervention remains difficult. Traditional clinical and anatomical factors do not always capture the underlying biology of metastatic disease. For the Minnesota patient, each decision followed clinical criteria. None could read the tumor.
PersonaDx is building the biological intelligence layer for metastatic cancer, bringing greater biological clarity to treatment decisions while establishing the foundation for a scalable platform across metastatic disease. Its lead assay, PersonaCRC, analyzes colorectal liver metastases to provide prognostic insights that can help oncologists make more informed, personalized treatment decisions.
“Precision oncology has transformed how we understand cancer, but the next frontier is metastasis,” says Kevin Donnelly, chief executive officer.
The Biology
In metastatic colorectal cancer, which commonly spreads to the liver, tissue from the colorectal liver metastasis undergoes RNA expression profiling. A neural network classifier analyzes the expression of 150 genes to classify the metastasis as canonical, immune, or stromal. PersonaCRC then integrates this molecular classification with established clinical factors to place the patient into a low-, intermediate-, or high-risk group. In the clinical cohorts studied, five-year survival was approximately 80 percent in the low-risk group, 60 percent in the intermediate-risk group and 40 percent in the high-risk group.
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Precision oncology has transformed how we understand cancer, but the next frontier is metastasis.
PersonaCRC builds on research published in Nature Communications and JAMA Oncology. A neural network classifier demonstrated >90 percent accuracy and was independently validated with Phase 3 New EPOC trial data. The resulting report provides oncologists with additional biological and clinical context when considering local therapy, systemic therapy, clinical trials, or other treatment approaches. PersonaCRC is intended to support, rather than replace, multidisciplinary clinical judgment.
While most precision oncology platforms identify targetable mutations, PersonaCRC is designed to characterize the underlying biology of metastatic disease and estimate which patients are most likely to benefit from potentially curative local therapies. This complements, rather than replaces, existing genomic testing.
The Foundation and Platform
PersonaDx co-founder Dr. Ralph Weichselbaum, a member of the National Academy of Medicine, helped establish the concept that metastatic disease exists along a biological spectrum and that some patients with limited metastatic disease may achieve long-term survival following local treatment. Co-founder and Chief Medical Officer Dr. Sean Pitroda led research defining the molecular subtypes of colorectal liver metastases and developing the integrated clinical-molecular classification underlying PersonaCRC.
PersonaDx is also researching how its approach may be extended to additional metastatic cancers, including renal cell, lung, pancreatic, breast and prostate cancers.
PersonaDx’s tissue-based prognostic approach may complement circulating tumor DNA technologies used to assess molecular residual disease. PersonaCRC provides biological and prognostic insight before treatment, while MRD technologies may help detect residual disease following treatment. Used at different points in the care pathway, these approaches could offer complementary insight into metastatic disease before and after intervention.
PersonaDx is also developing AI-enabled digital pathology to extend the same biological insights directly from routine H&E slides, enabling faster clinical decision support while keeping biology—not AI—as the central focus.
The Minnesota patient ultimately survived, but her experience illustrates the extraordinary clinical, personal and financial stakes involved when the likely behavior of metastatic disease remains uncertain. PersonaDx is working to provide oncologists and multidisciplinary care teams with deeper biological insight, beginning with metastatic colorectal cancer and expanding across additional tumor types. The company aims to transform metastatic tumors from anatomical findings into biologically understood diseases that support more precise treatment decisions. In recognition of this work, Life Sciences Review is naming PersonaDx one of its Top Metastasis Biomarker Solutions 2026.
Biology-Led Decisions in Metastatic Cancer Care
A metastatic lesion can place a treatment team between very different interventions while the available evidence still leaves the disease course uncertain. Surgery or ablation may offer curative potential for some patients. Systemic therapy may be more appropriate for others. The buying problem is not access to more data. It is whether a test can convert the biology of the metastatic site into guidance that makes the treatment discussion more informed before a major intervention is chosen.
Many precision oncology tools were built around primary tumors or actionable mutations. Those approaches remain useful, but they do not always explain the heterogeneity found after cancer has spread. A metastasis-focused biomarker should begin with tissue from the metastatic lesion rather than infer its behavior from the precursor tumor. Buyers should examine the biological signals being measured and the way clinical features influence the result. The classification must also reflect the metastatic disease and remain interpretable at the point of care. A technically advanced assay that answers the wrong biological question adds detail without reducing uncertainty.
"Risk labels have limited value unless they are tied to recurrence patterns and outcomes that can inform treatment planning."
Clinical validation bears equal weight. Risk labels have limited value unless they are tied to recurrence patterns and outcomes that can inform treatment planning. Evidence should show that the method distinguishes patients with materially different prognoses, not simply that it separates samples into statistical groups. Independent validation and peer-reviewed publication matter. Performance among cohorts must also be examined because treatment teams may use the result when considering invasive procedures or prolonged therapy. The closer a biomarker sits to a major intervention, the stronger its evidence base must be.
A useful report must also fit the way cancer care is decided. Oncologists rarely act on molecular data in isolation. Findings move through multidisciplinary review before treatment planning begins. Reports should make the risk classification understandable without reducing a complex tumor to a vague score. They should clarify what the result suggests about recurrence and how it may inform consideration of local or systemic treatment while preserving physician judgment. Turnaround time, sample requirements, report delivery and compatibility with present pathology processes affect whether the test reaches the tumor board in time to matter.
"Oncologists rarely act on molecular data in isolation. Findings move through multidisciplinary review before treatment planning begins."
Economic value follows clinical discrimination rather than broad promises of cost reduction. Avoiding an unnecessary transplant or an ineffective treatment course can reduce expenditure, but buyers should not treat savings as the primary proof of quality. The stronger case is a test that helps direct intensive treatment toward patients more likely to benefit and steers others away from avoidable burden. Payers and health systems can then assess financial impact against clearer treatment pathways rather than generalized efficiency claims.
PersonaDx developed PersonaCRC to provide metastasis-specific prognostic and treatment guidance for metastatic colorectal cancer. The assay combines RNA profiles from colorectal liver metastases with clinical features and applies an AI-based classifier to characterize tumor biology, stratify risk and inform treatment planning. Its underlying clinical-molecular approach was independently evaluated using data from the Phase 3 New EPOC randomized clinical trial and published in JAMA Oncology. The analysis builds on the premise that metastatic lesions carry biological information that the primary tumor alone may not detect. PersonaDx’s research discovers distinct metastatic colorectal cancer subtypes and links that biology with prognosis and treatment considerations. For multidisciplinary teams weighing local intervention versus systemic treatment, PersonaCRC supplies another layer of evidence to the decision while leaving final judgment with the treating oncologist.
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Metastasis Biomarker Solutions Info
Q1
What Are Biomarker Solutions for Metastatic Disease?
Metastasis Biomarker Solutions use biological information from metastatic tumors to add context that clinical and anatomical factors may not fully capture. In metastatic colorectal cancer, PersonaDx's PersonaCRC analyzes RNA expression from colorectal liver metastases and classifies the tumor as canonical, immune or stromal. The classification is combined with established clinical factors to place patients into low-, intermediate- or high-risk groups. This approach can provide prognostic insight that helps oncologists consider treatment choices alongside clinical judgment.
Q2
How Does PersonaDx Use Metastasis Biomarker Solutions in Metastatic Colorectal Cancer?
PersonaDx focuses on the biology of metastatic disease rather than looking only at anatomy or targetable mutations. Its lead assay, PersonaCRC, uses a neural network classifier to analyze the expression of 150 genes from colorectal liver metastases. The resulting molecular classification is integrated with clinical factors to estimate risk. This makes Metastasis Biomarker Solutions relevant when oncologists need a clearer view of how a metastatic tumor may behave and whether a patient may benefit from potentially curative local therapy.
Q3
What Clinical Insight Can Metastasis Biomarker Solutions Provide?
Metastasis Biomarker Solutions can add prognostic information before treatment decisions are made. In the clinical cohorts studied for PersonaCRC, five-year survival was approximately 80 percent in the low-risk group, 60 percent in the intermediate-risk group and 40 percent in the high-risk group. The classifier demonstrated more than 90 percent accuracy and was independently validated with Phase 3 New EPOC trial data. These findings are intended to give clinicians additional biological and clinical context when considering local therapy, systemic therapy, clinical trials or other treatment approaches.
Q4
How Does PersonaCRC Fit Into Existing Testing?
PersonaCRC is designed to complement rather than replace existing genomic testing. While many precision oncology platforms focus on targetable mutations, PersonaCRC characterizes the underlying biology of metastatic disease and estimates which patients may be more likely to benefit from potentially curative local therapies. This makes Metastasis Biomarker Solutions a different layer of information within the care pathway. The tissue-based approach may also complement circulating tumor DNA technologies that assess molecular residual disease after treatment, with each approach providing information at different points.
Q5
What Technology Is PersonaDx Developing Around Its Biomarker Approach?
PersonaDx is developing AI-enabled digital pathology to extend its biological insights from routine H&E slides. The goal is to support faster clinical decision-making while keeping the tumor's biology at the center. PersonaDx is also researching how its approach may extend beyond colorectal cancer to renal cell, lung, pancreatic, breast and prostate cancers. These efforts show how Metastasis Biomarker Solutions could be developed across additional metastatic cancers while retaining a focus on biological classification.
Q6
Why Do Metastasis Biomarker Solutions Matter for Treatment Decisions?
Metastasis Biomarker Solutions address the limited biological insight that can remain when treatment decisions rely mainly on clinical and anatomical factors. Metastatic disease accounts for approximately 90 percent of cancer-related deaths, yet determining which patients are most likely to experience durable outcomes after local intervention remains difficult. PersonaDx's approach adds biological information to that assessment. For complex interventions, this added context may help care teams identify patients who are more likely to benefit from local treatment and avoid treatments that are unlikely to provide durable benefit.
