Stock image of blood in a test tube

FREDERICK, Md. – Tissue biopsies are currently the norm for detecting and obtaining information about cancer. But this type of biopsy can be invasive, and not every patient can have one performed due to the location of their tumor or other health factors.   

In recent years, scientists have begun to explore measuring cancer mutations in the blood with liquid biopsies. Liquid biopsies are thought to have many advantages over tumor biopsies. These include the possibility to detect cancer early through a simple blood test, the ability to identify resistance to therapy before it can be seen by a radiographic scan, and the possibility of predicting patient response within only a short few weeks after treatment initiation by tracking early changes in tumor DNA levels in the blood. Liquid biopsy tests are based on the detection of what is known as circulating tumor DNA (ctDNA), which originates from dying tumor cells that spill their DNA into the peripheral blood.  

However, liquid biopsy research is still in its early stages, and as such, it requires validation to demonstrate its clinical effectiveness. Through a new collaboration with Illumina, the Molecular Characterization Laboratory (MoCha) at the Frederick National Laboratory for Cancer Research is working to address this critical need.

The multi-year collaboration, launched earlier this year, aims to provide a full analytical validation of Illumina’s TruSight Oncology (TSO500) assay, a blood-based test that is capable of identifying minute amounts of ctDNA. MoCha chose TSO500 to support several National Cancer Institute (NCI)-sponsored clinical studies after a rigorous review of a number of ctDNA assay platforms. 

“The TSO500 offers a breadth of coverage,” said Mickey Williams, Ph.D., director of the Molecular Characterization Laboratory. “Many more genes can be interrogated compared to other platforms.”

The assay obtains data from the full coding region of 523 genes in cancer-related pathways and can identify all major types of mutations that may occur in those genes. 

Importantly, the assay has high specificity, which means that it has a very low likelihood of falsely identifying a cancer mutation in a subject where there is none. The specificity of the assay aligns with its main intended use, which is to test several thousand plasma samples from the more than 5,600 patients screened for the NCI Molecular Analysis for Therapy Choice (NCI-MATCH) trial

MoCha plans to use TSO500 to obtain information about rare tumors, to determine how well tumor mutations identified from ctDNA match those identified in solid tumor tissue from the same patient, and to gather information about the ctDNA molecular profiles of patients treated with immune checkpoint treatments, which could provide value for immunotherapy studies. 

There will be three phases to the collaboration with Illumina. The first step is for MoCha to perform optimization and validation of the TSO500, which is already underway. The next phase, which is expected to last several years, will be clinical implementation of the assay. The final phase will involve providing genomic support for the NCI’s Experimental Therapeutics Clinical Trials Network (ETCTN), which will mainly be retrospective, examining plasma specimens and looking for candidate mechanisms of resistance and response to therapies. 

For the ETCTN trials, MoCha will be collecting blood throughout the course of a patient’s treatment for ctDNA analysis.  

“This will enable us to look at how patients progress and why,” explained Chris Karlovich, Ph.D., associate director of the Molecular Characterization Laboratory. 

MoCha staff will compare what they see in the ctDNA at the time progression occurred to what was present at the start of treatment.  

“We expect to see new mutations in the progression sample, which may tell us much about how specific cancer types evolve to become resistant to therapy, as well as inform the best choice for the next line of treatment,” explained Karlovich. 

For MoCha, the ongoing study will further evaluate the TSO 500 as a complement or potential alternative to tissue biopsies for genomic profiling of cancer patients. 

This work is scheduled to be presented at American Society of Clinical Oncology Annual Meeting in Chicago during a poster session on Saturday, June 1

By Max Cole, staff writer