Blood Testing Technology May Yield Better Information Than Tissue Biopsies for Cancer

Known to be present in the blood of cancer patients for decades, cell-free DNA (cfDNA) may make tumor biopsies a relic of the past, say researchers at Georgetown Lombardi Comprehensive Cancer Center

Tumor biopsies are currently a mainstay of most cancer treatments and normally involve surgically taking a small sample of the tumor. This sample is then analyzed under a microscope and through laboratory testing to determine tumor-specific characteristics that ultimately guide diagnosis and treatment.

While tumor biopsies have generally yielded helpful information, this technique of examining a cancer has weaknesses. One weakness is that tumors may not be the same throughout the entire tumor, or have different traits depending on the area of the body it is in. Additionally, biopsying a tumor carries risks of infection and other risks that can occur from the process of taking the biopsy.

Important for patient care and considered the gold standard for detecting and obtaining information about cancer, tissue biopsies can be invasive, risky, costly, and painful. Thus, these and other factors have led researchers to explore alternative approaches such as liquid biopsy.

Liquid biopsy, while still evolving, has greatly expanded and could potentially impact patient care in significant ways, perhaps soonest with metastatic breast cancer or non-small cell lung cancer (NSCLC). Liquid biopsy is a complementary technique to standard tissue biopsies. It takes and analyzes nonsolid biological tissue obtained from blood and most other bodily fluids. Among the benefits are the rapid and noninvasive methods involved.

Georgetown Research Exploring cfDNA for Utility

Evaluating better ways to analyze tumors, researchers from Georgetown University Medical Center recently published a study in Frontiers in Genetics that will be of interest to oncologists and bioinformaticists. The study explores cell-free DNA (cfDNA), DNA that is released into the bloodstream during normal cell death.

While cfDNA was discovered back in the 1940s, recent advances in genetic sequencing technology have enabled this form of DNA to provide more valuable information. Ranging from sequencing techniques to PCR-based methods and other more complex strategies, cfDNA analysis is poised to become a reliable and sustainable diagnostic, prognostic, and predictive tool in cancer care and management.

The Georgetown cfDNA analysis study points to certain modifications to DNA, called methylations, that allow researchers to identify what type of cell the DNA came from. This method of DNA analysis enabled the researchers to analyze the genetic makeup of multiple healthy and tumor cells from a single blood draw.

Anton Wellstein, MD, PhD (above), of the Wellstein Lab at Georgetown University’s Lombardi Comprehensive Cancer Center, studies cellular, molecular, and biochemical signal transduction mechanisms in vitro as well as in tumors. Wellstein’s lab is credited with defining the role of secreted binding proteins for FGF (FGFBPs) in cancer, physiology and development. Wellstein and others are now studying the value of cell-free DNA analysis (cfDNA) as a possible alternative to standard tissue biopsy in cancer testing. (Photo: Lombardi Comprehensive Cancer Center)

“Taking tumor tissue biopsies is a hit or miss process and is usually not a good representation of the whole tumor or its spread,” explained Anton Wellstein, MD, PhD, Professor of Oncology and Pharmacology at Georgetown Lombardi and corresponding author for the study, in a recent press release. “Using blood, or liquid biopsies, on the other hand, provides a homogeneous representation of cfDNA that is being shed from all types of cells.”

While cfDNA was discovered decades ago, genetic sequencing tools and computational technology has only recently provided the advances necessary for this type of research. “Fine-tuning these applications of cfDNA analysis is challenging and requires in-depth approaches, both at the genome sequencing level and computationally,” said Megan Barefoot, an MD/PhD student in the Wellstein lab at the Cancer Center and lead author of the article.

“Methylated cfDNA has opened a new and minimally invasive way to detect damage to cells in the body as there are often hundreds of methyl markers per cell that can mark, very specifically, where the cells came from, much like a barcode scanner at a grocery checkout tells the store the identity of a particular product,” Barefoot continued. “Combined biological and computational analyses make deciphering these methylation patterns/molecular barcodes possible so that researchers can trace the origins of cfDNA.”

cfDNA Key to Assessing If Cancer Therapy Is Effective?

While cfDNA analysis can be used to provide information about the genetics of tumors, it can also provide valuable, personalized data about cancer treatment efficacy. As cancer treatments lead to the death of tumor cells, and potentially healthy cells, data from cfDNA analysis can provide information about which cells are being killed by the treatments.

“This approach can be applied to any therapy that will impact tissue equilibrium by causing cells in tissues to become damaged and die, including chemotherapy, radiation, and immunotherapy. This review really helps set the stage for our future research efforts,” said Wellstein. “My lab is very actively pursuing methods and technologies that further refine analyses of methylated cfDNA.”

Wellstein expressed expectations that this technology will become a routine method of testing cancers in hospital laboratories. “We believe these efforts are affordable and will soon become standard in labs and they should make a difference in advancing the understanding and treatment of many cancers.”

Circulating Biomarker Research Will Continue

Hospital and oncology group leaders should anticipate more to come from cfDNA analysis studies in cancer management. Providing information about disease progression and therapy response in real-time, cfDNA analysis could not only become routine as part of cancer testing but may even displace standard tissue biopsies.

Cell-free DNA analysis may also be useful in monitoring any therapy that causes cells in tissues to become damaged and die. 

The lower expense and decreased risks combined with better, individualized data make cfDNA analysis a disruptive technology that is likely to become an important component of precision medicine cancer treatment.

—Caleb Williams

Related Information:

DNA tags enable blood-based tests to assess cancer treatment outcomes

Private payer and Medicare coverage for circulating tumor DNA testing: a historical analysis of coverage policies from 2015 to 2019

Detection of Cell Types Contributing to Cancer From Circulating, Cell-Free Methylated DNA

Liquid biopsy and tumor heterogeneity in metastatic solid tumors: the potentiality of blood samples

Georgetown Lombardi Comprehensive Cancer Center

Challenges and opportunities of cfDNA analysis implementation in clinical practice: Perspective of the International Society of Liquid Biopsy (ISLB)

Megan Barefoot

Anton Wellstein, MD, PhD

The Promise of Liquid Biopsies for Cancer Diagnosis

FDA Oncology Center of Excellence

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