Liquid Biopsy for Brain Tumor Biomarker Detection Developed
Mutations in the DNA, changes in epigenomic makeup, and variations in gene expression associated with brain tumors can inform clinical practice by providing invaluable information for diagnosis, prognostication, disease monitoring, and development of personalized treatment strategies.
Such molecular biomarkers, which can be examined in surgical resection or biopsy specimens, are becoming an integral component of clinical practice. However, direct surgical tissue biopsy to determine tumor molecular profiles is associated with potential complications such as hemorrhage and infection.
Therefore, scientists at the Washington University are now developing a technique that allows them to detect brain tumor biomarkers through a simple blood test.
Liquid biopsies are a hot field, with several companies, including Foundation Medicine and Grail, either marketing tests or working to develop them. Such tests are designed to pick up in the bloodstream small pieces of DNA shed by cancerous tumors — information that then can be used to treat and monitor the disease.
Currently, doctors largely use surgical biopsies for information about a tumor’s genetic mutations and whether the cancer can be treated with available drugs. But such biopsies are invasive and can be expensive and painful. In addition, patients aren’t always healthy enoughto undergo them, and sometimes not enough tissue is procured to allow pathologists to conduct high-level analysis.
Hong Chen, a biomedical engineer, assistant professor of biomedical engineering in the School of Engineering & Applied Science and of radiation oncology in the School of Medicine, said while researchers have already learned how to get a drug through the blood-brain barrier into the brain via the bloodstream, no one — until now — has found a way to release tumor-specific biomarkers — in this case, messenger RNA (mRNA)— from the brain into the blood.
“I see a clear path for the clinical translation of this technique,” said Chen, an expert in ultrasound technology. “Blood-based liquid biopsies have been used in other cancers, but not in the brain. Our proposed technique may make it possible to perform a blood test for brain cancer patients.”
The blood test would reveal the amount of mRNA in the blood, which gives physicians specific information about the tumor that can help with diagnosis and treatment options.
The method allows biomarkers from a brain tumor to pass through the blood-brain barrier into a patient’s blood through the use of targeted ultrasound and microbubbles.
The technique, which was tested in 12 mice models, allowed messenger RNA to pass through the brain into the blood. Something never done before, according to authors.
Scientists experimented on mice using two different types of the deadly glioblastoma brain tumor. They focused on the tumor utilizing centered ultrasound, a strategy that utilization ultrasonic vitality to target tissue somewhere down in the body without entry points or radiation. Like an amplifying glass that can center daylight to a small point, centered ultrasound concentrates ultrasound vitality to a minor point profound into the cerebrum.
When they had the objective — for this situation, the mind tumor — specialists at that point infused microbubbles that movement through the blood like red platelets. At the point when the microbubbles achieved the objective, they popped, causing minor breaks of the blood-mind obstruction that permits the biomarkers from the cerebrum tumor to go through the hindrance and discharge into the circulatory system. A blood test can decide the biomarkers in the tumor.
The team continues to work to refine the process. The future will require integration with advanced genomic sequencing and bioinformatics to enable even more refined diagnostics.