A simple blood test that detects chemical changes in DNA identified more than 90% of stage 2-4 lung cancers in an early study, without relying on costly DNA sequencing.
Researchers at Tel Aviv University and collaborating medical centers have developed a blood test for lung cancer that analyzes chemical patterns on fragments of DNA circulating in the bloodstream. The test focuses on DNA methylation, a type of chemical tagging that can influence gene activity without changing the DNA sequence itself. Because cancer cells often carry distinctive methylation patterns, fragments of DNA they release into the blood can provide a recognizable molecular signature.
To detect that signature, the researchers extract cell-free DNA from a blood sample, chemically process it, amplify selected regions, and use an engineered enzyme to attach fluorescent markers to methylated sites. The labeled DNA is then placed on a hybridization microarray and scanned optically. The resulting light pattern can reveal whether the sample carries a methylation profile associated with lung cancer.
How the Lung Cancer Test Performs
In the study, which included 103 people, researchers compared samples from 51 lung cancer patients with those from 52 healthy controls. After developing a diagnostic signature based on 170 genomic regions, they tested it on a separate blinded validation group. For patients with stage 2-4 lung cancer, the method reached 93.1% sensitivity and 90.3% specificity.
The researchers also found that the DNA patterns differed between adenocarcinoma and squamous cell carcinoma, the two major forms of non-small cell lung cancer. That raises the possibility that the same underlying technology could eventually provide information about tumor type rather than simply flagging whether cancer is present.
Lung cancer remains an enormous global health problem. The latest GLOBOCAN estimates indicate that about 2.6 million people were diagnosed with lung cancer worldwide in 2024, and roughly 1.9 million died from it, making it both the most commonly diagnosed cancer and the leading cause of cancer death globally.
Why Blood Testing Could Improve Lung Cancer Screening
Low-dose CT scans can save lives by detecting lung tumors earlier. Large randomized trials have found that CT screening reduces lung cancer mortality among people at elevated risk. But screening also has an important drawback: suspicious lung nodules are common, and many are not cancer. Depending on the trial and criteria used, false-positive rates have been substantial, sometimes leading to further scans and invasive procedures.
A reliable blood test could therefore have value alongside imaging, potentially helping doctors decide which suspicious findings deserve closer investigation. The researchers envision their technology as a complement to CT rather than a replacement for it.
The method also sidesteps another obstacle facing some blood-based cancer tests. Many liquid biopsies depend on next-generation sequencing and extensive computational analysis, which can increase cost and limit how easily the tests can be deployed. The new assay instead relies on fluorescent labeling and microarray technology that the researchers say could be used in standard clinical laboratories.
The test currently takes about two to three days and costs approximately $60 per sample, according to the researchers.
Tracking Whether Lung Cancer Treatment Is Working
The study also offered an intriguing glimpse of another possible use: tracking whether therapy is working.
Among the patients evaluated over time, changes in DNA methylation patterns mirrored what doctors saw on medical imaging. When patients responded to treatment, their molecular profiles shifted toward those of healthy participants. In patients whose tumors did not respond, researchers saw no comparable change.
If that finding holds up in larger studies, blood sampling could potentially provide doctors with another way to monitor treatment response. The researchers stress, however, that this part of the work remains preliminary.
What Still Needs to Be Proven
Despite its potential relevance to earlier diagnosis, the strongest reported performance in this study was for stage 2-4 cancers. The research was also a proof-of-concept study involving only 103 participants. Much larger and more diverse trials will be needed to determine how well the test performs in stage 1 disease, in people undergoing routine screening, and in patients with other conditions that might alter DNA methylation.
The research was led by Prof. Yuval Ebenstein of Tel Aviv University in collaboration with scientists and physicians from JaxBio Technologies, Bnai Zion Medical Center, Sheba Medical Center, and other institutions.
Prof. Ebenstein concludes, “Our goal is to make blood tests for cancer diagnosis more accessible, simpler, and less expensive without compromising accuracy. We have developed a new approach that does not require genetic sequencing but instead identifies the tumor’s chemical ‘fingerprint’ with light, using a technology that can be implemented in standard clinical laboratories. This is a significant step toward developing a tool that can complement imaging tests and help physicians diagnose lung cancer and monitor treatment effectiveness.”
Reference: “Sequencing-free On-chip detection of lung cancer by fluorescent enzymatic profiling of cfDNA methylation” by Abed Agbarya, Noa Gilat, Yael Michaeli, Jasline Deek, Assaf Grunwald, Sivan Yogev, Lynne Itelson, Suheil Artul, Rasha Khoury, Michael Peled and Yuval Ebenstein, 11 June 2026, npj Precision Oncology.
DOI: 10.1038/s41698-026-01547-2
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