Blood tests can tell us a lot about what’s going on in our bodies—from whether we’re eating too much sugar to whether we’re harboring any infectious diseases. Scientists lately have been working on ways to use similar diagnostic tools for cancer, which have the potential to dramatically increase the amount of information doctors use to figure out the best treatments for their patients.
Called liquid biopsies, these tests are designed to pick up genetic material shed by cancer tumors into the blood, which lets doctors avoid the invasive procedures needed to extract samples directly from tumors. That advantage over tissue-based biopsies is especially important in cases where tumors are deeply embedded in internal organs, and hard to reach. For now, the blood-based tests are not used to screen for cancers in healthy people but to guide treatments in those who are already diagnosed. A biopsy, whether from the tissues or the blood, can provide genetic clues about the mutations that are driving the tumors, and can direct doctors to the best drugs for treating them.
That’s why these tests have developed in tandem with drugs designed to specifically block the effects of certain mutations that help cancers grow, and have made a huge difference in the world of cancer treatment. Matching these so-called targeted therapies to the right tumor mutations can improve survival rates for patients with lung and breast cancers, among others.
Earlier this summer the U.S. Food and Drug Administration approved a blood-based test from Guardant Health to track 55 genetic mutations in any solid cancer. The agency also approved the use of the Guardant test as a so-called companion diagnostic, meaning its results could be used to direct doctors to a specific drug, osimertinib, made by AstraZeneca, to treat certain lung cancers. The FDA also this summer approved a liquid biopsy test from Foundation Medicine that analyzes more than 300 cancer-related genes.
These tests build on earlier generation versions that were approved by the FDA and scanned blood for a limited number—often even single—mutations. The new ones pick up fragments of DNA shed by dying or dead tumors into the blood; these fragments are analyzed to see if there are any matches with a larger number of common mutations known to drive tumor growth.
Dr. Edward Garon is an associate professor of medicine at University of California, Los Angeles, and an oncologist who treats lung cancer patients. Blood-based biopsies of lung tumors, he says, make it possible for him to keep closer tabs on how his patients are doing—since they are far less invasive and less dangerous than a biopsy procedure, liquid biopsies can be done much more regularly. This gives him a better sense for how patients’ tumors are changing, and possibly even developing new mutations to resist the medications he gives them. “Liquid biopsies at this point have become part of our standard practice,” Garon says.
And because liquid biopsies represent the universe of genetic changes shed by tumor cells, they may have yet another advantage over tissue biopsies. When doctors perform a tissue biopsy, they can generally only sample one or a limited number of sites in a tumor at a time. But tumors often possess more than one genetic mutation that fuel their growth. Because many of these genetic fragments will end up in the bloodstream, liquid biopsies may be able to pick up more genetic mutations wherever they are in the tumor.
The liquid biopsies may also provide results faster than tissue-based tests. After doctors send Guardant blood samples, for example, the company takes about six days to sequence the tumor DNA it contains and provide a report on which mutations it found. “Sometimes that’s faster than the analysis that can be done from a tumor biopsy,” says Garon. Foundation Medicine’s test takes one to two weeks, according to the company.
Dozens of anti-cancer drugs that are designed to target specific genetic mutations behind abnormal growth are now available, but only about a quarter of cancer patients get detailed genetic testing of their tumors. Many instead get tests that look for single genetic mutations, (such as the BRCA 1 and 2 mutations that contribute to breast cancer) but in-depth profiling can give a much more accurate picture of which mutations are behind a patient’s cancer, and which drugs might be best to treat it. While education among both doctors and patients about the benefits of such genetic profiling is growing, many doctors are still unsure of how to interpret the results and how best to apply them to treat patients in a more precise way, which is slowing uptake.
The data on how and when liquid biopsies can be useful to guide treatments are growing, as are studies on when liquid biopsies might be sufficient and when they need to be supplemented with tissue biopsies. Though still incomplete, these data are encouraging. For example, a 2019 study led by researchers at University of Texas MD Anderson Cancer Center looked at 282 patients with metastatic non-small-cell lung cancer (NSCLC) who had both a traditional tissue biopsy and gave blood for the Guardant Health liquid biopsy test. It found that the Guardant test picked up signs of tumor mutations in 77 patients, while the tissue biopsies detected these in 60. The liquid biopsy also provided results in an average of nine days compared to 15 days for the tissue-based tests.
In another study, Johns Hopkins researchers found that blood-based tests could detect NSCLC patients’ response to treatment anywhere from four to nine weeks before CT images of the lung could. Those weeks are critical for cancer patients whose tumors may be developing resistance to their current therapies, and who could potentially get a step ahead of their cancer if that resistance, in the form of new mutations, is picked up sooner rather than later.
But the field of liquid biopsy is still young, and questions about the accuracy and reliability of the tests remain. While a positive test result means that the mutations it picked up are most likely present—which also means doctors can generally treat their patients based on that information—negative results are trickier to interpret. Because the blood tests rely on finding fragments of DNA shed by tumors, and amplifying them, it’s possible that negative results aren’t actually negative, but mean instead that there wasn’t enough DNA material to work with. “Not all tumors have the same amount of circulating tumor DNA,” says Garon. “So a negative test for a gene mutation does not definitively rule out the idea that a mutation is present.” That’s when a tissue biopsy could be ordered to verify the result.
Nevertheless, liquid biopsies are already reducing the need for invasive tissue biopsies and giving doctors a way to better track their patients’ progression. Ultimately, say officials from both Guardant and Foundation Medicine, the goal is to look to the blood not only as a guide for which drugs to use for which patients, but to screen for cancer at even earlier stages, before it’s diagnosed. Grail, an Illumina spinoff that is poised to go public, is focusing its efforts on such screening, and published data from thousands of patients showing its test can pick up 50 different cancers. If it becomes as easy to pick up tumors from a blood test as it is to learn your cholesterol levels, then it may be possible to get ahead of new cancers so they don’t progress into serious and advanced disease when they’re harder to treat.