Doorways to Discovery
November 11, 2014
Today’s big advances in medicine are built on a foundation of past discoveries, new technologies and forward thinking. At the Ludwig Center at Johns Hopkins, all the parts are coalescing into major gains for diagnosing and controlling cancer. The latest is a liquid biopsy, “a noninvasive way of monitoring a person’s cancer status,” typically by using the patient’s blood, explains Johns Hopkins neurosurgeon Chetan Bettegowda.
“Our research is focused on understanding the genetic makeup of a tumor. Once we know it, we can search for a particular DNA biomarker in a patient’s blood and use that signature to quantify the cancer, decide on the best treatment, and monitor the patient over time for drug resistance and other responses,” he says.
The liquid biopsy concept has been around for more than a decade, but until now, clinicians have largely relied on protein biomarkers rather than DNA biomarkers, which have many potential applications. For example, researchers showed about 10 years ago that several cancers, including malignant melanoma, contain a faulty version of a protein called B-Raf. Drugs were developed to inhibit the mutant B-Raf. “That was a big step forward,” says Bettegowda. “But tumors almost always will find a way to become resistant to the drug. Having a liquid biopsy can help detect the resistance that is forming and allow physicians to change treatment in real time.”
As a neurosurgeon, Bettegowda is focused on a unique aspect of a liquid biopsy for brain cancers. “Brain cancers do not shed much DNA into the blood, probably because of the natural blood-brain barrier,” he explains. The Ludwig Center researchers and worldwide collaborators are working to detect brain cancers in cerebrospinal fluid (CSF) instead, via a spinal tap.
Bettegowda wants to avoid surgical procedures whenever possible. He envisions, for example, using a CSF liquid biopsy for brain tumor patients who develop treatment side effects that mimic tumor progression. “We’d spare the patient going into surgery for a biopsy of the tumor itself.”
The researchers haven’t completely ruled out a blood-based liquid biopsy for analyzing brain tumors and responses to treatment. Blood- and CSF-based liquid biopsies are being researched in parallel. “We expect to develop new ways of detecting molecules of DNA from nervous system cancers that could show up in blood,” says Bettegowda.
Doorways to Discovery: Liquid Biopsy to Track Cancer (View Video)
Challenge: To accurately track whether brain tumors are growing or receding without resorting to surgical biopsy.
Approach: Bettegowda is testing a “liquid” biopsy, using body fluid.
Progress: Tests are being developed to track cancer-specific DNA in CSF and blood.