Blood Test Detects Early Cancers, Tracks Treatment Resistance, and Identifies Tissue Damage

Researchers at Stanford Medicine have created a blood test that can detect various forms of cancer, how tumors resist therapies, as well as tissue damage resulting from non-cancerous ailments.

The updated test examines RNA molecules present in the bloodstream. These RNA molecules are referred to as cell-free RNA since they no longer reside within cells. Blood consistently contains snippets of both DNA and RNA—which originate from the normal process of cellular decay occurring across various tissues and organs throughout the body, including potentially cancerous tumors.

Over a span exceeding six years, the researchers crafted innovative techniques aimed at targeting messenger RNA within blood samples. They subsequently employed these methods for detecting various stages of cancer, assessing resistances developed against cancer treatments, and evaluating the extent of damage inflicted upon healthy tissues.

"Similar to how archaeologists gain insights into past civilizations from examining their discarded refuse, we can glean significant information regarding cellular activities within a patient’s body by analyzing the fragmented RNA molecules that circulate via the bloodstream,” explained co-senior author Maximilian Diehn, MD, Ph.D., who holds the position of Jack, Lulu, and Sam Willson Professor at Stanford Medicine and serves as a professor of radiation oncology. “Our team has created an advanced form of liquid biopsy capable of detecting both free-floating and tumor-derived RNA. This innovation could potentially improve personalized treatment strategies for various conditions including cancers and non-cancerous disorders.”

A paper explaining the method and applications of the cell-free RNA blood test was published in Nature On April 16, 2025, Monica Nesselbush—a postdoctoral researcher at the Stanford Cancer Institute—Bogdan Luca—who works as a postdoctoral fellow in pathology—and Young-Jun Jeon—an ex-postdoctoral research associate from Stanford Medicine who has since become a faculty member at Sungkyunkwan University—are listed as shared first authors. The investigation was jointly overseen by Ash Alizadeh, M.D., Ph.D.—the Moghadam Family Chairholder and an educator in both medicine and disciplines such as oncology and hematology—in collaboration with Diehn.

Identifying Cancers and Resistance to Treatment

The amount of cell-free RNA circulating in the bloodstream is minimal, with approximately 95% consisting of ribosomal RNA that forms part of the cellular machinery responsible for protein synthesis. This novel blood test focuses on analyzing messenger RNA, which comprises only a small fraction—less than 5%—of the total cell-free RNA. These mRNA molecules act as indicators of gene expression into proteins.

The research team limited their examination of gene activity to roughly 5,000 genes that aren’t commonly expressed in the bloodstream of individuals who are healthy. Concentrating on what are known as low-abundance genes enhanced the accuracy of the test significantly—by more than fiftyfold—in detecting cancer. This method allowed the test to detect lung cancer RNA in 73 percent of those with lung cancer, even when diagnosed at an early stage.

"By analyzing these rarely abundant genes, we can concentrate on the most pertinent segment of RNA to identify diseases, much like how archaeologists aiming to understand ancient diets would zero in on specific artifacts such as food vessels or tools," explained Alizadeh.

Identifying cell-free messenger RNA implies that the blood test can track conditions unrelated to genetic mutations, which form the core of most DNA-based diagnostics, for instance, some factors contributing to treatment resistance in cancers.

"Regrettably, a considerable number of our patients receiving treatment for cancer eventually find that their therapy becomes ineffective. This resistance frequently arises from alterations in cell behavior or appearance rather than through genetic modifications," noted Alizadeh.

Our non-invasive method could potentially eliminate the need for surgical biopsies and help detect these frequent types of resistance at an early stage, even before they appear on scans or cause symptoms such as pain. This allows for earlier intervention and adjustment of treatments, which can enhance overall outcomes.

Discovering a biomarker from what is stored in the freezer

Prior to enabling the research group to extract data from circulating messenger RNA within the bloodstream, they needed to mitigate the impact of platelets—cells crucial for blood clotting that carry RNA yet lack DNA. These platelets can distort test outcomes and mask indicators related to cancer. Consequently, the scientists devised an integrated approach combining both molecular techniques and advanced computation designed specifically to neutralize interference stemming from these abundant cellular elements.

The computational technique for addressing platelet contamination ensures effectiveness not only with freshly drawn blood specimens but also with those that were previously collected and preserved.

By adopting this method, we can analyze blood samples already stored in freezers from concluded clinical trials, as an illustration, and potentially identify a molecular profile that distinguishes responders from non-responders to specific medications," explained Diehn. "This allows us to expedite our search for such markers, which can subsequently be utilized immediately when treating current patients.

Tip of the iceberg

The novel cell-free RNA technique also offers valuable insights beyond cancer-related uses. In tests, elevated amounts of healthy lung RNA were identified in plasma samples taken from individuals who required intubation and ventilation due to acute respiratory distress syndrome, a critical ailment that extensively harms the lungs and leads to cellular death.

The level of typical lung RNA present in the blood samples of COVID-19 patients correlated with their severity of illness. Additionally, the study revealed that this type of RNA was detected in the bloodstream of healthy individuals who smoke, potentially suggesting subtle damage to the lungs due to smoking.

The researchers from institutions including Massachusetts General Hospital, Harvard Medical School, Memorial Sloan Kettering Cancer Center, Fred Hutchinson Cancer Center, and the University of Washington were contributors to this study as well.

More information: Monica C. Nesselbush and colleagues presented an ultra-sensitive technique for detecting cell-free RNA. Nature (2025). DOI: 10.1038/s41586-025-08834-1

Furnished by Stanford University Medical Center

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