Using Cell-free DNA as a Biomarker

The potential uses of cfDNA as a biomarker are especially relevant to NSCLC due to the difficulties of collecting sufficient tumor tissue. This has stimulated interest in analyses using serum and plasma samples which contain cell-free DNA originating from tumor tissues. Detecting somatic mutations from plasma DNA in advanced cancer patients may be preferable when repeated tumor biopsies are not feasible and genomic analysis of archival tumor is deemed insufficient.

Overall, testing cfDNA has four distinct advantages over conventional biopsies of which I’ve produced an infographic below highlighting these:

Putting it into context: Non-small Cell Lung Cancer

The fight against lung cancer is an important part of the battle against cancer overall.  Lung cancer is the leading cause of cancer-related deaths worldwide with over 1.1 million patients and 1.2 million new cases of lung cancer diagnosed every year.

Non-small-cell lung cancer accounts for about 87% of all lung cancers and includes: squamous cell carcinomas, adenocarcinomas and large cell carcinomas. Within these tumors, EGFR mutations occur in approximately 10-15% of patients in Europe and 30-40% in Asia.

It has been hypothesized that a large proportion originates from malignant cells that are constantly going through growth/remodeling/apoptosis/necrosis and subsequently releasing digested or possibly metastatic/pathogenic nucleic acids into the blood . Although it is not clear, we have known for more than 30 years that cell-free DNA concentration is elevated in malignancy (nearly 4 times), and moderately elevated in benign disease, as compared to controls.

Overall, testing cfDNA has four distinct advantages over conventional biopsies, being:

•       Cost-effective approach;
•       Simplified sample collection procedures;
•       Reduced impact to the patient and;
•       Easily analyzed.

Crucially, the combination of these advantages allows for repeat routine testing of the patient through diagnosis to efficacy of treatment.

“cfDNA shows promise as an indicator (biomarker) of cancer and is easily accessible, reliable and reproducible”

Challenges facing cfDNA Detection

The advantage of cfDNA analysis are clear, however, the clinical feasibility of using cfDNA to detectEGFR mutations was assessed a recent phase III study of a Japanese subset of patients. The study identified that the proportion of patients identified with mutant EGFR was lower when assessed in cfDNA (23.7%) compared with tumor tissue (61.5%). Although cfDNA results identified no false positives, a high rate of false negatives (56.9%) was observed.

What do you think? Is cfDNA the next big thing? Comment below!