A groundbreaking study published in Nature on April 16, 2025, unveils a novel cell-free RNA blood test that promises to revolutionize the early detection of cancers, monitoring of treatment resistance, and assessment of tissue damage. Joint first authors Monica Nesselbush, Bogdan Luca and Young-Jun Jeon had collaborated intensely. They worked closely with world-renowned Stanford Medicine professors Maximilian Diehn and Ash Alizadeh, both co-lead authors.
This groundbreaking blood test takes a new approach by looking at messenger RNA (mRNA). It represents less than five percent of total cell-free RNA detected in the blood. By honing in on this small subset of RNA, the researchers hope to better detect the different stages of cancer. It serves to identify tumors and monitor resistance to existing cancer therapies. Additionally, it tracks what degree of harm is inflicted on non-cancerous tissues.
Understanding the Mechanism
So, the research team focused their deep-learning efforts on about 5,000 genes that are only occasionally expressed in the bloodstream of healthy people. The test’s specificity for correctly identifying cancer improved greatly through this concentration on these “rare abundance genes.” In doing so, their specificity increased more than 50-fold, letting them detect with unprecedented precision bitterness at the molecular level.
“Analysis of the rare abundance genes lets us focus on the most relevant subset of RNA for detecting disease, just like archaeologists who want to learn about what people ate might focus on a subset of artifacts such as food containers or utensils,” – Ash Alizadeh.
The study’s results found the blood test was able to accurately identify RNA of lung cancer in 73% of patients. This means everyone, including those with early stage disease diagnosed at present day. This figure is a stark reminder of the need for early and accurate diagnosis and intervention.
Monitoring Treatment Resistance
As impressive as the cell-free RNA blood test is in accurately diagnosing cancer, its most important work may be in treating resistance. This is what makes it an indispensable tool for cancer patients. Traditional approaches have difficulty in detecting evolutionary changes that are not associated with genetic mutations. Instead, they often miss important shifts in cell function.
“Unfortunately, a significant fraction of our patients who are being treated for cancer go on to have their therapy stop working, and that resistance is often based on adaptations that do not involve genetic changes,” – Ash Alizadeh.
With this new method, clinicians are able to assess adaptations sooner. This gives them the ability to intervene with treatment sooner than traditional scans or symptoms would otherwise permit.
“Our non-invasive approach has the potential to avoid surgical biopsies and identifying these common types of resistance earlier before substantial disease burden shows up on scans or presents with symptoms like pain,” – Ash Alizadeh.
Advancing Personalized Medicine
The implications of this research extend beyond oncology. The cell-free RNA blood test may enhance personalized medicine strategies for both cancerous and non-cancerous diseases. This approach to liquid biopsy is remarkably flexible. This design measures both circulating tumor RNA and non-tumor cell-free RNA.
“We have developed a sensitive, versatile new type of liquid biopsy that measures cell-free and circulating-tumor RNA and has the potential to enhance personalized medicine in cancer and non-cancer diseases,” – Maximilian Diehn.
This advancement could streamline diagnostics and improve patient outcomes by allowing clinicians to make informed decisions based on real-time data, which could ultimately lead to better therapeutic strategies tailored to individual patients.
“We can save time by using historical samples to discover a biomarker that can then be applied in real time to patients moving forward,” – Maximilian Diehn.