Closer to a Blood Test for MPNST: New Results from a Major CTF-Funded Research Project

What if a simple blood test could help doctors detect one of the most dangerous cancers associated with NF1, potentially earlier than they can today?

That has been the goal of a major research effort supported by the Children's Tumor Foundation since 2022. Led by Angela Hirbe, MD, PhD, of Washington University School of Medicine; Jack Shern, MD, of the National Cancer Institute; and Aadel Chaudhuri, MD, PhD, now at Mayo Clinic, the project is developing a liquid biopsy, a blood test that searches for tiny fragments of DNA released by tumors into the bloodstream.

Now, a new publication in npj Precision Oncology marks an important milestone in that work. The research team reports that an improved version of its blood test was able to distinguish people with malignant peripheral nerve sheath tumors (MPNST) from people with benign plexiform neurofibromas and people without tumors. The test also showed potential for monitoring MPNST over time, including detecting evidence of one patient's recurrence before it was clinically diagnosed.

It is an encouraging step toward a goal CTF and its research partners have been pursuing for years: giving people with NF1 and their doctors a better way to detect and monitor these aggressive cancers.

The challenge of detecting MPNST

People with NF1 can develop plexiform neurofibromas (PN), tumors that grow along nerves and are generally benign. In some cases, however, tumors can transform into MPNST, an aggressive form of cancer.

Determining when that transformation has occurred can be difficult.

Doctors currently rely on a combination of symptoms, imaging, and, when appropriate, tumor biopsy. But distinguishing a benign tumor from one that is becoming malignant isn't always straightforward, particularly in people who may have many tumors throughout their bodies.

Earlier and more reliable detection could make a critical difference. Finding an MPNST while it is smaller and localized may provide a better opportunity for successful surgical removal and other treatment.

That's why researchers have been asking whether some of the information they need could instead be found in a patient's blood.

Looking for signs of cancer in the bloodstream

Tumors can release small fragments of their DNA into the bloodstream, known as circulating tumor DNA, or ctDNA.

In 2022, CTF committed nearly $2 million to a three-year collaborative project led by Drs. Hirbe, Shern, and Chaudhuri to build on promising early evidence that ctDNA could help distinguish MPNST from benign plexiform neurofibromas.

The vision was ambitious: develop a relatively simple, minimally invasive blood test that could help identify malignant transformation earlier and eventually provide doctors with a new way to monitor people at risk for MPNST.

CTF stepped in to support the project after an earlier funding proposal received strong scientific reviews but could not be fully funded. Rather than allow promising work to slow or stop, CTF committed to moving the project forward.

The study was structured around the collaborative principles of CTF's Synodos research model, bringing researchers together to share data and expertise while keeping the needs of people living with NF at the center of the work.

A more powerful blood test

The new publication represents an important advancement in that effort.

Earlier approaches primarily examined changes in the number of copies of sections of DNA found in the bloodstream. For this study, the researchers developed a more comprehensive test that integrates multiple types of genetic changes associated with MPNST.

The team evaluated the approach in 82 participants, including people with MPNST, people with benign plexiform neurofibromas, and tumor-free controls.

The integrated test performed substantially better at distinguishing MPNST from the other groups than the researchers' previous approach.

In other words, by looking at several different kinds of tumor-related DNA signals together, researchers were able to get a clearer molecular picture of whether MPNST was present.

Could a blood test also help monitor cancer?

The study also provides an intriguing glimpse of another potential use for liquid biopsy: monitoring what happens after an MPNST has been treated.

Researchers were able to track tumor-related DNA over time in some participants. In one case, the blood test detected molecular evidence of a patient's MPNST recurrence 80 days before the recurrence was clinically diagnosed. In another, tumor DNA cleared from the bloodstream in a way that was consistent with lasting remission.

These are individual examples, not yet evidence that the test can reliably predict recurrence for everyone. But they illustrate what could eventually be possible.

A future blood test might not only help doctors identify whether a suspicious tumor has become malignant. It could potentially help them follow how someone is responding to treatment or look for signs that cancer has returned.

From an ambitious idea to measurable progress

When CTF announced its investment in this project in 2022, Dr. Shern described a long-term vision: a blood test routinely used in the NF clinic to detect tumor progression.

This new publication does not mean that the test is ready for routine clinical use. The assay still requires additional validation in larger and independent groups of patients before it could become part of standard NF care.

But it represents meaningful progress toward that vision.

CTF invests in research with the potential to change what is possible for people with NF, and then works to keep promising science moving forward. In this case, that meant recognizing an opportunity when other funding fell short, bringing researchers together around a shared goal, and making a significant investment in the development of a tool that could ultimately change how one of the most serious complications of NF1 is detected and monitored.

There is still work to do. But the possibility that a blood test could one day help doctors find MPNST earlier, monitor treatment, and detect recurrence sooner is getting closer.

Read the research

The study, Integrated multiclass driver ctDNA profiling enables MPNST detection and monitoring in NF1 patients, was published in npj Precision Oncology in July 2026.

Read the new study in npj Precision Oncology

Read CTF's 2022 announcement of the biomarker project