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  • A MagSifter chip used to extract CTCs from blood samples(Credit: Seung-min Park)

    Targeting the primary tumor has long been the approach of traditional cancer treatments. However what causes death is actually metastasis, i.e. the process by which cancer cells spread to other parts of the body. Since metastatic cancer cells can differ genetically from those found in the original tumor, treatment that focuses on the latter has little effect on them. Enter a new blood test developed by Stanford researchers to single out circulating tumor cells (CTCs), which have been identified as a key agent of metastasis. Not only could it help doctors make better prescriptions without resorting to invasive procedures like biopsies, it could also help patients avoid breaking the bank with its under-US$30 pricetag.

    When tumor cells enter the bloodstream, it’s only a matter of time before they take root in another organ and initiate the growth of a new tumor there. The presence of CTCs in the bloodstream is thus generally bad news for cancer patients as they indicate a high possibility of metastasis. Scientists on the other hand believe that there is a silver lining to their presence, especially if they can be isolated and their genetic profiles evaluated. Instead of second-guessing how the tumor is changing and prescribing ineffective therapies, blood-based monitoring could help doctors select the most appropriate personalized treatments based on this data.

    “Without a biopsy and genetic profiling, we are flying blind, trying to select a second or third option for therapy and hoping it works,” says lead author Seung-min Park. Lung biopsies, in particular, can take a toll on a patient’s already weakened body.

    That said, finding CTCs in the bloodstream is akin to searching for legs on a snake. Not only are they rare – in a single milliliter of blood, there are fewer than ten of them to the several billion red blood cells – they are also hard to isolate. To do so, the Stanford researchers used antibodies to identify the malignant cells. Once labelled with the antibodies, the researchers then attached magnetic nanoparticles to the cells, which enabled them to extract the CTCs from the blood samples using a device called a magnetic sifter, or MagSifter.

    After the cancer cells are fished from the blood, they are placed in an array, which a Stanford article on the technique describes akin to a muffin pan, where each cup holds a single cell. Once the cells are placed in the array, which holds 25,600 of them, they can then undergo genetic analysis.

    The new blood test requires no more than two milliliters of blood (roughly half a teaspoon), costs less than $30 and can be completed in about five hours. In comparison, a lung biopsy with DNA sequencing can cost up to $18,000 and take as long as three weeks to deliver results. CellSearch, currently the only US Food and Drug Administration (FDA)-approved CTC test on the market, only assesses patients with metastatic breast, prostate, or colorectal cancer and costs about $900. Results are usually delivered within a week.

    While the MagSifter was used to test lung cancer cells, the researchers say it can be used on other kinds of cancer as well. “We validated our device on lung cancer because of the difficulties of doing lung biopsies. But the technology is not limited to profiling lung cancer. We could swap out markers and adapt the technique to other types of cancers,” says former PhD student Dawson Wong, who was also part of the study.

    If approved by the FDA, the new technique could make a huge difference in cancer care in two ways. First, by helping doctors evaluate the cells’ response to chemotherapy and indicating which drugs to prescribe when they develop resistance to a prescribed treatment. Secondly, by allowing them to study how tumors evolve.

    “We feel that we have solved a lot of the technical hurdles,” said Wong. “The blood draw is cheap enough and noninvasive enough that it could be done on a weekly basis throughout treatment.”

    The results of their study were published in Proceedings of the National Academy of Sciences.

     

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