While many individuals with early-stage non-small cell lung cancer (NSCLC) are successfully treated with surgery, radiation therapy, systemic therapies, or a combination of these approaches, recurrence remains a frequent concern. Depending on the stage and other factors, roughly 1 in 4 patients with Stage I disease may experience a recurrence, which is why regular follow-up imaging and survivorship care are so important.
Dr. Ignaty Leshchiner, a cancer researcher from Yale University and Yale Cancer Center, previously Boston University and recipient of the American Lung Association Innovation Award, is working to address this concern. His research focuses on finding extremely small traces of cancer that may remain in the body even after effective treatment is complete. By using advanced blood tests, his research team hopes to detect returning cancer much earlier than current methods allow.
If successful, this work could help doctors make more informed treatment decisions, improve clinical trial design and participation, and give patients a better chance of receiving timely treatments if their cancer returns.
A Career Focused on Understanding Cancer
Dr. Leshchiner has spent more than 15 years studying how cancer changes over time and how it becomes resistant to treatment. He has worked on and led several research projects involving different cancer types, including lung cancer, and has developed methods to study the genetic changes that happen as tumors grow and evolve.
One area that has particularly interested him is understanding why some cancer cells survive treatment while others die. "We developed methods to model clonal evolution and modeling resistance and genetic changes after treatment across multiple cancer types," Dr. Leshchiner explained. "In the future, we also will develop methods for what we call modelling progression trajectories." In other words, we will be able to predict when the cancer will come back before progression is apparent in the clinic.
The Challenge of Determining Cancer Recurrence
Lung cancer occurs when abnormal cells grow uncontrollably and form tumors in the lungs. If not detected and treated early, the cancer can spread to other parts of the body and cause symptoms such as persistent coughing, wheezing, chest pain, and coughing up blood. After treatment, including surgery when appropriate, imaging tests such as PET and CT scans are commonly used to monitor for signs that the cancer has returned. However, even when treatment is successful and no cancer is visible on scans, a small number of cancer cells may sometimes remain in the body. Dr. Leshchiner and others refer to this remaining cancer as "minimal residual disease" (MRD).
Because these cells are too small to appear on imaging tests, they may lay undetected for years until they begin growing again. Dr. Leshchiner's research aims to identify these leftover cancer cells long before they become visible on imaging tests. "Without the high sensitivity methods we are developing, there's really no way of knowing if the tumor is returning or if it's been cured," he said.
Using a Blood Test to Track Cancer
Instead of relying only on scans, Dr. Leshchiner's team wants to use a simple blood sample to look for remaining signs of cancer.
As cells die, they release small pieces of DNA into the bloodstream known as cell-free DNA. Cancer cells also release DNA, and researchers can look for clues within those fragments to determine whether cancer is still present in the body.
Dr. Leshchiner's team studies both genetic changes and methylation, a process in which tiny biological markers are added to DNA. These markers can help identify which organ or location the DNA came from, and whether it originated from a tumor. These methylation patterns are highly specific to different tissues and cancers, allowing researchers to distinguish between cancer DNA and normal DNA circulating in the blood.
The ultra-sensitive testing methods Dr. Leshchiner's team developed can detect tumor DNA at incredibly low levels, giving doctors earlier warning that cancer is returning. "We can follow each patient's tumor at a very high accuracy down to 10 to the minus 6 levels, so one in a million molecules in the blood," he said.
Monitoring Patients After Treatment
This approach does not rely on a single blood test. Instead, patients are monitored over months or years. Researchers begin by taking a biopsy of the original tumor and sequencing it. Then, they collect blood samples before and after surgery, and at regular follow-up visits. By comparing samples over time, researchers can see how tumor DNA levels change.
"If the tumor is not fully removed and if it's growing back as a recurrence, that tumor DNA level slowly starts to increase," explained Dr. Leshchiner. "This means you can catch cancer coming back or cancer that is not responding to treatment very early."
The team can also examine whether different groups of cancer cells are resisting treatment. Some cancer cells may carry genetic changes that make them unresponsive to certain drugs. Understanding those differences could help doctors choose more effective treatments in the future.
A New Way to Measure If a Treatment Works
One of the most promising parts of the research is its potential to show whether treatment is working much sooner than current methods can tell us.
When treatment successfully kills or removes cancer cells, tumor DNA may briefly increase in the bloodstream as the cancer cells disappear. But over time, those levels should fall if treatment is working. "As the patient responds, the DNA level drops off slowly and gets to zero if they're fully responding," Dr. Leshchiner said.
This could give doctors a new way to track a patient's cancer without waiting for changes to appear on imaging scans. In some cases, it may even help reveal disease that has spread beyond the lungs but remains too small to be seen with traditional imaging methods.
The Future of Lung Cancer Treatment
Dr. Leshchiner believes these blood-based monitoring tools could have a major impact on the future of lung cancer care.
Today, many clinical trials must follow patients for years before researchers know whether a new treatment is helping prevent cancer from returning. This process can be lengthy and expensive. He hopes that minimal residual disease testing can help determine treatment effectiveness sooner and more simply. "We're hoping in the near future to be able to use these methods to accelerate approval and development of cancer drugs," he said.
For patients, earlier detection of returning cancer may allow doctors to intervene sooner. Patients whose blood tests show no remaining cancer cells might avoid unnecessary treatment, while those at higher risk of recurrence could receive additional therapies before visible tumors develop.
Most importantly, this research focuses on people with earlier-stage lung cancer, when treatment has the best chance of success. By helping doctors identify lingering disease earlier and evaluate treatments more quickly, Dr. Leshchiner's work could bring more effective therapies to patients sooner and improve the chances of long-term survival. While more research is still needed, his work offers an exciting glimpse into the future of lung cancer care.
Learn more about our lung cancer research at Lung.org/research.
Blog last updated: November 11, 2026
