Hebrew University and NIH team tracks small-cell lung cancer burden from 1 mL of blood plasma in an observational study

An international team led by Prof. Nir Friedman and Dr. Gavriel Fialkoff of the Hebrew University-Hadassah Medical School, with Dr. Nobuyuki Takahashi and Dr. Anish Thomas of the US National Cancer Institute (NIH), has developed a blood-based method to track small-cell lung cancer. The study, published in the Journal of Clinical Investigation and described by eurekalert.org, analyzed 441 plasma samples from patients with small-cell lung cancer, people with other cancers and healthy individuals eurekalert.orgeurekalert.orgeurekalert.orgOpen source ↗.

Small-cell lung cancer accounts for approximately 15% of lung cancer cases. It often grows and spreads quickly, and many patients are diagnosed at an advanced stage. Tumors typically shrink under treatment and then return. Examining what has changed may require a repeat tissue biopsy, which is difficult in these patients and can hasten disease progression.

cfChIP-seq: reading gene activity in blood

The team used a technique called cfChIP-seq. Dying cells release fragments of DNA wrapped around histone proteins into the bloodstream, and chemical marks on the histones show which genes were active in the cells of origin. Many existing liquid biopsies look for changes in the DNA sequence; this approach instead looks at how cells use that sequence. The assay needed about one milliliter of plasma.

The authors identified molecular patterns characteristic of small-cell lung cancer and built a quantitative score of the strength of these cancer-associated signals. They also compared blood findings with gene activity measured in tumor samples eurekalert.orgeurekalert.orgeurekalert.orgOpen source ↗.

Tumor burden and subtypes

The score correlated with the amount of cancer measured by medical imaging and changed during treatment. Across the patients studied, the median score fell after treatment, consistent with reduced tumor mass. Higher scores were associated with shorter survival in the study group.

The blood samples also carried information on molecular subtypes. Signals in a patient's blood closely reflected the activity of key genes in that patient's tumor tissue. Some samples showed signals linked to more than one subtype. Because blood can collect material shed by cancer cells at different sites, the authors note the approach may give a broader view than a biopsy from a single site.

The method is not yet ready to replace tissue biopsies or guide routine treatment decisions. Larger studies are needed to establish how reliably it tracks changes and whether using its results to choose treatments improves patient outcomes eurekalert.orgeurekalert.orgeurekalert.orgOpen source ↗.