A new method to noninvasively diagnose cancer and monitor its progression could eliminate the need for painful and sometimes life-threatening biopsies. Fragments of RNA that cells eject in fatty droplets may point the way to a new era of cancer diagnosis, potentially eliminating the need for invasive tests in certain cases.
Cancer tumor cells shed microvesicles containing proteins and RNA fragments, called exosomes, into cerebral spinal fluid, blood, and urine. Within these exosomes is genetic information that can be analyzed to determine the cancer’s molecular composition and state of progression. Researchers at Massachusetts General Hospital discovered that exosomes preserve the genetic information of their parent cells in 2008, however exosomes have not seen widespread clinical testing as a means of cancer diagnosis until now.
“We have never really been able to detect the genetic components of a tumor by blood or spinal fluid,” says Harvard University neurologist Fred Hochberg. “This is really a new strategy.” He says exosome diagnostic tests could potentially detect and monitor the progression of a wide variety of cancers. He is one of the lead researchers in a multicenter clinical study using new exosomal diagnostic tests developed by New York City-based Exosome Diagnostics to identify a genetic mutation found exclusively in glioma, the most common form of brain cancer.
When treating other forms of cancer, surgeons are able to biopsy tumors to diagnose and monitor the state of the disease. For brain cancers like glioma, however, multiple biopsies can be life threatening. Bob Carter, head of neurosurgery at the University of California, San Diego, says well-preserved RNA in blood and spinal fluid enables researchers to test and monitor for these genetic changes noninvasively.
He says study researchers separate exosomes from bio-fluids with a diagnostic kit and then extract the relevant genomic information. Once the specific cancer mutation is identified, clinicians will periodically draw additional bio-fluids to monitor the mutation levels to determine whether a patient is responding to therapy.
Whereas Magnetic Resonance Imaging (MRI) is a useful tool, tumors only show up on imaging scans once they are at least one millimeter in diameter and comprise about 100,000 tumor cells. By that time, it may be too late for an early intervention. On the flip side, MRIs can also yield false positives. Hochberg says individuals who have been treated with conventional radiation therapy often have benign residual tissue from dying tumor cells that have been killed by the treatment but which the body has not yet eliminated. This tissue is often mistaken for tumor growth on a MRI scan. “You would identify to the patient that the drug is not working when in reality it is doing well,” Hochberg says. “On the other hand, having an easily accessible biomarker for glioma would give you a clear response.”