Fragments of RNA that cells eject in fatty droplets may point the way to a new era of cancer diagnosis, potentially reducing the need for invasive tests. Cancer tumor cells shed so-called exosomes, fatty droplets that contain proteins and RNA fragments, into cerebral spinal fluid, blood and urine. Within these exosomes is genetic information that scientists can analyze to determine the cancer's molecular composition and state of progression. Researchers at Massachusetts General Hospital discovered in 2008 that exosomes preserve the genetic information of their parent cells. But they have not seen widespread clinical testing as a means of cancer diagnosis until now.
“This is really a new strategy,” says Harvard Medical School neurologist Fred Hochberg, one of the researchers in a clinical study using new exosomal diagnostic tests to identify a genetic mutation found exclusively in glioma, the most common form of brain cancer. Hochberg and his colleagues plan to present preliminary results from the pilot study, which involves 18 U.S. hospitals, in April at a symposium in Boston.
When treating many forms of cancer, surgeons are able to biopsy tumors to diagnose and monitor the state of the disease. For brain cancers such as glioma, however, multiple biopsies can be life-threatening. Bob Carter, head of the study and of neurosurgery at the University of California, San Diego, Medical Center, says study researchers separate exosomes from biofluids with a diagnostic kit and then extract the relevant genomic information. Once the specific cancer mutation is identified, clinicians periodically draw additional biofluids to monitor the mutation levels and determine whether a patient is responding to therapy.
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“What we are trying to finalize are the sensitivity and specificity of the test,” he says. Exosome diagnostics could also be used in conjunction with current methods, such as prostate-specific antigen (PSA) tests for prostate cancer. The combination would help physicians determine the nature of a tumor and what type of treatment it warrants. “If someone has a high PSA and also has biomarkers that are positive in exosomes, that would be a great test,” says Sudhir Srivastava, head of the National Cancer Institute's Cancer Biomarkers Research Group.