‘Liquid biopsies’ could revolutionize cancer detection
In the next year or two, doctors will begin routinely monitoring cancer using a potentially revolutionary technique that searches for a genetic signature in a blood sample, according to experts in the field.
MILWAUKEE — In the next year or two, doctors will begin routinely monitoring cancer using a potentially revolutionary technique that searches for a genetic signature in a blood sample, according to experts in the field.
The new method, known as a "liquid biopsy," holds the promise of detecting the reappearance of cancer much earlier and more accurately than current methods. And in years to come, this method could also provide a better, less invasive way to diagnose disease than a tissue biopsy.
"This is a very important development that has the potential to transform the way that we see cancer and the way that we treat it," said Steve Shak, chief scientific officer for Genomic Health, a Redwood City, Calif., company that has been testing liquid biopsy techniques and plans to bring one to a clinical trial in 2016. While some of the early liquid biopsy studies have been in breast and prostate cancer, Shak added, "this is a technology we believe will have an impact on all tumor types."
So far the technique has been used on a relatively small number of cancer patients. Biocept, a San Diego, Calif., firm, performs liquid biopsies on patients with breast, lung and gastric cancers; the company had completed about 400 of the biopsies by the end of 2014. Michael Nall, Biocept's president and chief executive officer, said the technique also offers doctors a better way to detect when a patient's cancer has spread to areas that are more difficult to access for tissue biopsies.
Nall said researchers hope the new biopsy method will translate into longer survival rates for various cancers, though he cautioned, "at this point there's more research that needs to be done to prove that."
Medicine currently struggles when it comes to monitoring cancers. For prostate cancer, doctors measure what's called the prostate-specific antigen (PSA), a protein that's used as a surrogate for the volume of cancer.
"The problem is that some cancers as they devolve stop making PSAs," said William See, chairman of urology at Froedtert and the Medical College of Wisconsin. "PSA is a protein that's regulated by a lot of things. You can make the PSA go way down and still have lots of cancer."
And for the vast majority of cancers, there isn't even an equivalent to the PSA. Instead, doctors must monitor the progress of disease using radiography, such as MRI and CT scans. These methods generally don't detect tumors until the growths reach a sufficient size, about 1 cubic centimeter.
Liquid biopsies, however, take advantage of the fact that when cells die, as they do routinely, they release DNA into the bloodstream. The DNA of a tumor cell is markedly different from normal DNA. See was encouraged by a recent report in the journal Clinical Chemistry, in which scientists at Vanderbilt University found that a liquid biopsy was significantly better than the PSA method at distinguishing between patients with prostate cancer and healthy patients.
Local scientists are among those testing different liquid biopsy methods.
"The most important things in cancer is early diagnosis," said Liang Wang, an associate professor of pathology at the Medical College of Wisconsin. "If this can be developed it would be a very powerful technology."
Wang has been researching two different methods of liquid biopsy, one using DNA circulating in the bloodstream, the other using RNA embedded in vesicles, tiny membranes released by cells.
So far, his results in lung, prostate and colon cancer indicate that the circulating DNA could be an effective test for early detection and for predicting the outcome of treatments.
As for the RNA method, a paper he published in 2014 in European Urology found strong evidence that it could be an effective test for monitoring advanced prostate cancer.
Wang said that reading the genetic signature from a blood sample also offers an important advantage over solid biopsies of a tumor. Different parts of a tumor may have different genetic variants, meaning that a biopsy offers only a snapshot of the cancer. Blood, however, provides doctors with a global picture of the cancer, since it contains DNA from all over the tumor.
Liang Cao, a staff scientist at the National Cancer Institute, said the new liquid biopsies will better enable doctors to monitor the changes occurring in a patient's cancer in real time. When a patient is taking a chemotherapy drug, the treatment sometimes kills some of the tumor cells while sparing others. As a result the cancer evolves, assuming the identity of the survivor cells and becoming more and more resistant to the specific chemo.
"Two to three years down the road if cancer recurs, the recurrent tumor can be very different from the original tumor," Cao said. "DNA will allow you to get a real-time look."
Using next generation sequencing machines to get more detailed DNA readings from blood may be expensive at first, but the cost of the technology has been dropping swiftly. And doctors point to the potential for huge savings. At present, a cancer patient can easily spend $8,000 to $10,000 on a medication that may no longer be helping.
"Right now," said Shak at Genomic Health, "we're flying blind with cancer for many patients."
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