A novel technique to detect very low levels of cancer cells in blood could provide an easier and more effective way to monitor progression of the disease. The inexpensive microfluidics device, designed by researchers at Massachusetts General Hospital (MGH), in Boston, might eventually be used to tailor cancer treatments to individual patients by monitoring cancer cell counts and by identifying the molecular attributes of an individual’s cancer.
Malignant tumors continually shed cancer cells into the bloodstream, and these cells can spread the disease to other tissues. This process, known as metastasis, is the deadliest aspect of cancer: it is the culprit in nine out of ten cancer deaths. But the circulating tumor cells are so rare–with a concentration of onlyone in a billion cells in the bloodstream–that scientists haven’t been able to detect them easily or accurately enough to be clinically useful. Now Mehmet Toner, a bioengineer at MGH and Harvard Medical School, and his colleagues have designed a microfluidics device that can analyze whole blood in large enough volumes to detect these scarce cells.
“I think this device is going to turn the field of metastasis upside down,” says Toner, who led the work. “It finds the circulating tumor cells that end up killing people.” He adds that the sensitivity of the test is “high enough for clinical applications.”
The device consists of a business-card-size silicon chip dotted with 80,000 microscopic posts. Each post is coated with a molecule that binds to a specific protein found on most cells originating from solid tumors, such as breast, lung, or prostate cancer. As blood flows through the chip, tumor cells stick to the posts.
See how the microfluidics chip works.
Initial tests show that the device is highly sensitive. An analysis of blood samples from 68 patients with five types of cancer detected cancer cells in all but one sample, according to findings published today in the journal Nature. Researchers also found that changes in the number of circulating cancer cells accurately reflected changes in the size of patients’ tumors during treatment. Oncologists often use tumor size as a measure of how well a treatment is working, with the goal of shrinking the tumor.
Such blood tests could ultimately prove to be an inexpensive and noninvasive complement to the CT scans and tissue biopsies that oncologists traditionally use to characterize tumors. For example, regular blood tests assessing tumor cell count might be used to determine if a particular treatment is effective. That might allow “the treatment regimen to be modified much earlier than if physicians had to rely solely on changes in tumor size,” says Jonathan Uhr, a scientist at the University of Texas Southwestern Medical Center, in Dallas, who wrote a commentary accompanying the paper in Nature.
Toner likens the circulating tumor cell count to viral loads in HIV, which doctors use to assess how effective antiviral drugs are. “If we’re going to turn cancer into a chronic disease, we need to monitor the patient accordingly,” he says.
Researchers can also examine the cells captured on the chip for molecular markers that suggest a more aggressive form of cancer or a tumor that will respond to specific cancer drugs. The researchers ultimately hope to use the chip to analyze genetic changes in the tumor, which might signal the need to change treatments.
The ability to monitor changes in the levels of circulating tumor cells might also reshape physicians’ view of cancer. For example, a preliminary study of patients with prostate cancer showed that a subset of people diagnosed as having localized cancer actually had circulating tumor cells. “It may be that cancer needs to be defined more molecularly than morphologically,” says Toner.
Scientists caution that extensive research needs to be done before the device can be used for routine clinical monitoring. The chip is now being tested in larger clinical trials of lung and prostate cancers to determine how to best use it in cancer treatment.