Blood Test Offers New Way to Track Lung Cancer

Anish Thomas, MD, the Roswell Park Professor of Hematology and Oncology. — Anish Thomas, MD, the Roswell Park Professor of Hematology and Oncology, was senior author of the study.

Northwestern Medicine scientists and collaborators have demonstrated a novel liquid biopsy technique that can measure cancer burden and reveal molecular characteristics of small cell lung cancer (SCLC), according to a new study published in the Journal of Clinical Investigation.

The new approach could eventually allow clinicians to monitor how the disease changes during treatment through a simple blood test, according to the study’s senior author Anish Thomas, MD, the Roswell Park Professor of Hematology and Oncology.

“Although SCLC has historically been treated largely as a single disease, we now recognize that there are important biological differences between tumors,” said Thomas, also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “Understanding these differences is essential to developing more effective treatments.”

Small cell lung cancer accounts for roughly 15 percent of lung cancer cases, according to estimates from the Centers for Disease Control and Prevention, and is marked by rapid growth, early spread and poor survival outcomes. Although scientists have identified molecular subtypes of the cancer with distinct biological characteristics, obtaining enough tumor tissue for molecular testing has remained a persistent challenge.

To address this challenge, investigators collaborated with Nir Friedman, PhD, and his research group at the Hebrew University of Jerusalem, who pioneered a technique called cell-free chromatin immunoprecipitation sequencing (cfChIP-seq). Investigators demonstrated that cfChIP-seq could identify key gene-expression features of SCLC using as little as 1 milliliter of blood.

Investigators analyzed 441 plasma samples from patients with SCLC and other cancers, as well as healthy controls, and compared blood-based findings with matched tumor samples. The results showed that cfChIP-seq could measure tumor burden, track cancer progression and identify molecular subtypes of SCLC without requiring repeated tissue biopsies.

“SCLC presents a unique challenge,” Thomas said. “Most existing liquid biopsy technologies are very good at detecting DNA mutations, but in SCLC, much of the important biology is driven by differences in gene expression rather than mutations. These differences define molecular subtypes of the disease and may reveal vulnerabilities that could be exploited to develop new treatments.”

Unlike conventional liquid biopsies that focus primarily on tumor DNA mutations, cfChIP-seq examines DNA fragments and associated proteins shed into the bloodstream by dying cells. By analyzing active chromatin marks, investigators can determine which genes are turned on within tumor cells.

The investigators found that their blood-based SCLC score correlated strongly with cancer burden shown on tumor imaging.

“A particular strength of our study was the availability of matched blood and tumor samples from several patients,” Thomas said. “This allowed us to validate the blood-based measurements against gene expression in the tumors themselves.”

The findings could have important clinical implications. Repeat biopsies are often impractical in patients with recurrent SCLC, as the disease can progress rapidly and require immediate treatment.

“A blood test that captures both tumor burden and molecular identity could eventually help clinicians monitor treatment response, detect changes in tumor biology as resistance develops, and better understand which patients may benefit from future therapies,” Thomas said.

Although the results are encouraging, larger prospective studies are needed before the technology can be incorporated into routine clinical care, Thomas said. Future research will focus on repeatedly sampling patients during treatment to determine whether blood-based molecular signatures can predict treatment response and resistance.

“We are interested in determining whether we can detect changes in tumor biology as cancers respond to treatment and subsequently develop resistance,” Thomas said. “We also want to evaluate whether these molecular signatures can help identify patients most likely to benefit from new treatments being developed for SCLC.”

“Our hope is that approaches like this will help bring precision medicine to SCLC, where it has been particularly challenging,” Thomas said.

The study was supported by the National Institutes of Health Intramural Research Program (NCI ZIA BC 011793), the European Research Council, the Israel Science Foundation, the Israel Precision Medicine Partnership, the Israel Ministry of Health and European Union Horizon 2020.

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