Ignaty Leshchiner, PhD

Monitoring the recurrence and progression of lung cancer, particularly in high-risk populations like smokers, is critical to improving patient outcomes. Current methods often rely on imaging studies, which typically detect recurrence at later stages, limiting treatment options. At the same time, identifying subtle genetic changes that signal renewed disease activity can help physicians intervene sooner and more precisely. Recent advances in analyzing cell-free DNA—tiny fragments of genetic material released into the bloodstream—offer an opportunity to monitor cancer non-invasively and at earlier timepoints. Our project focuses on developing highly sensitive methods to detect and track these tumor-related DNA fragments when they are present at extremely low levels. By measuring growth rates of different types of cancer cells shedding this DNA directly we can predict the time when the cancer will come back and what characteristics the recurrent or metastatic tumor will have.

Update; During the first year of this project, we developed new approaches to detect very small amounts of lung cancer DNA that remain in the blood after treatment. Our work combines highly accurate DNA sequencing with methylation patterns that help identify whether cell-free DNA comes from lung tissue or other parts of the body. We also advanced a computational framework to model rare cancer cell populations, estimate how they change over time, and identify subclones that may be growing or shrinking during minimal residual disease.  This is important as recurrence may be driven by small resistant subclones that begin expanding before disease is detectable by imaging. Together, these efforts provide the foundation for a more sensitive and informative blood-based approach to lung cancer monitoring. Our long-term goal is to detect recurrence earlier, understand how residual cancer evolves after treatment, and ultimately support clinical strategies that allow intervention before relapse becomes clinically apparent.