When 49-year-old Star Dolbier landed at the University of Maryland Greenebaum Cancer Center in the summer of 2018 with a large mass on her left lung, she’d done enough research to know the situation was dire. The five-year survival rate for her type of advanced lung cancer—the most common among patients like herself who had never smoked—was 6 percent . Plus, she’d likely have to go through a painful biopsy surgery—in which doctors remove tissue from her lung through her chest wall—and wait weeks for the results.

So when she met with her new oncologist, Dolbier was surprised to learn that the medical center was part of a research trial that would analyze tiny fragments of cancer DNA that the tumor had shed in her blood. The results of the new test made by a company called Guardant Health in Silicon Valley came back within a week. They revealed that she was part of the 15 percent of lung cancer patients with a mutation in their EGFR gene, which made her eligible for a new drug treatment that been approved just four months earlier for patients with advanced non-small cell lung cancer.

The drug is part of a new generation of targeted therapies that work according to patients’ unique biology. Partially thanks to such drug therapies, the American Cancer Society announced earlier this year the biggest single-year drop in cancer mortality, between 2016 and 2017. In particular, people are dying less from lung cancer, which is the leading cause of cancer deaths and in 2019 killed nearly 143,00 people in the United States.

A year and a half later, Dolbier’s new drug has kept her cancer at bay.

“I’m living a normal life life right now because we were able to find out I had a specific mutation and that there was a specific drug I could take,” says Dolbier, who lives in Ellicott City, Maryland.

Dolbier is a poster child for the potential of precision medicine in oncology—the rapidly expanding field in which doctors use insights from patients’ DNA to better understand what drives their disease and prescribe personalized drug treatments, rather than resorting to a one-size-fits-all standard of care. Last year saw the approval of more than two dozen such drugs, and over the next two years, analysts predict that the number of new personalized treatments will outnumber those for the general population. As of 2020, there are now targeted therapy drugs for 30 kinds of cancer.

As part of this whirlwind of innovation, more cancer centers are setting up genetic sequencing labs, and more oncologists are advising patients to get their tumor tissue genetically sequenced. Yet scientists are also hoping to learn the deeper secrets of cancer from our blood, which they believe offers more comprehensive information about the complexity of a patient’s cancer.

“A tumor might tell you one thing, however not all tumors in the body have the same genetic alterations, and they’re constantly mutating in response to treatments,” says Pasi Jänne , a medical oncologist at Dana-Farber Cancer Institute in Boston. “Tumors can spit out genetic information into the blood and provide a summary of what’s happening in the total body in all the different cancers. The direction of where treatment goes might be dictated by that.” Jänne explained there are currently five approved precision medicines for genetic subtypes of lung cancer.

“The existing technology we have available is imaging scans and surgical tissue biopsies. Both are powerful but limited,” says Viktor Adalsteinsson , associate director of the Gerstner Center for Cancer Diagnostics at the Broad Institute in Cambridge, Massachusetts. “Imaging can’t see the smallest cancers and can lead to inconclusive results. Surgical biopsies are invasive and painful and can’t be done repeatedly throughout care.” Never mind that up to 30 percent of patients with non-small cell lung cancer don’t have enough tissue for standard testing, according to a 2018 study in Nature Medicine.

In addition to identifying patients’ genetic mutations to select treatment, oncologists are looking in their blood post-surgery to see if all the cancer was removed during an operation. “Traditionally, we have no reliable way of knowing if the surgery got it all,” Adalsteinsson says. “This poses a major challenge because we don’t know which patients have residual cancer could benefit from additional treatment, such as chemotherapy or radiation.” The new technology aims to identify a returning cancer’s DNA presence long before a new tumor grows big enough to be seen again on a conventional scan and when treatment is likely to be more effective.

But the biggest advance the field has been waiting for is the ability to detect cancer in the very early stages. If the technology can be developed, a blood test could be part of annual physical exams to tell us when cancer cells first appear in the body, when it’s most treatable. The 2016 launch of GRAIL, a Silicon Valley startup founded to develop such early-detection technology, was so celebrated that it has raised more than $1.6 billion in venture capital, backed by technology magnates such as Jeff Bezos and Bill Gates.

Although GRAIL’s first product is still a couple years away from reaching doctors’ offices, more than 50 companies are now working in the so-called “liquid biopsy” market that’s expected to reach $3 billion by 2024. The earliest commercial use of genetic sequencing occurred about a decade ago for what’s now widely known as the “non-invasive prenatal test.” Sequencing machines could analyze fetal DNA in the mother’s blood and detect a baby’s risk of Down syndrome in addition to several other genetic disorders as early as nine weeks into a pregnancy. Scientists also discovered the technology could flag maternal cancers.

The Swiss pharmaceutical company Roche was the first to receive FDA approval in 2018 for a liquid biopsy test to identify a lung cancer mutation to select patients for a new drug. Some of the newest entrants are taking advantage of advances in next-generation sequencing to go bigger by looking at many genes and many cancers at once.

In October, Guardant submitted for FDA approval its Guardant360 test that analyzes more than 70 cancer genes to determine treatment, and the company is working on another product for cancer recurrence and last fall launched a study for early detection in colorectal cancer patients. A 2018 JAMA Oncology study of non-small cell lung cancer patients who underwent tissue and blood tests found that the Guardant test picked up important mutations for 82 patients, compared to tissue alone for 47 patients. That same year, Boston-based genomic testing company Foundation Medicine received the FDA’s “breakthrough device” designation to expedite approval of a liquid biopsy test that will analyze 324 genes and biomarkers to inform treatment for metastatic cancer patients.

Scientists at Frederick National Laboratory for Cancer Research in Frederick, Maryland, and Providence St. Joseph Health Molecular Genomics Laboratory in Portland, Oregon, are launching studies on a new test developed by San Diego genetic sequencer manufacturer Illumina that analyzes 523 genes in key cancer-related pathways. And Epic Sciences of San Diego is developing liquid biopsy tests that will track the genetic changes occurring as cancer cells evolve over time. That knowledge would alert oncologists when patients become resistant to particular therapies and should switch treatments.

“The ability to detect the mechanisms that could lead to resistance may be better in the blood than in tissue. Looking at the blood is a pool of all the metastasized sites,” says P. Mickey Williams , director of the molecular characterization laboratory at the Frederick National Laboratory for Cancer Research. A 2019 study in Nature Medicine of 42 patients with gastrointestinal cancer found that liquid biopsies were superior in detecting such resistance, when compared to analyzing tissue samples of multiple tumors which had grown genetically diverse in the same patient. The insight, say experts, explains why some patients become resistant to targeted therapies that might have worked beautifully for them in the beginning.

Despite the promise of how liquid biopsies can transform cancer care, some experts say the technology still has some kinks to be worked out, especially when it comes to early detection. For example, not all cancers shed DNA the same way in the blood, and signs of those cancers might be hard to pick up, says Carlo Bifulco , a molecular pathologist at Providence Cancer Institute in Portland, Oregon. The other challenge is that genetic sequencing technology is so sensitive it can identify genetic mutations in healthy people that aren’t a threat to their health.

“How many false alarms will happen?” asks Eric Topol , director of the Scripps Research Translational Institute in La Jolla, California. “We have so many mutations in our cells, but so few of those become cancer. I don’t want them to lead to a lot of unnecessary anxiety and big expensive diagnostic evaluations.” Topol says a more practical approach would use genetic testing to identify patients at high risk and then use blood tests to further screen them. “People die of cancer when it spreads. If you could get to it in the microscopic stage, well before there was any mass that could be seen by a medical scan, that may well be a great story. But we’re not there yet.”

Yet according to GRAIL’s leadership, we’re really close—as in only a year or two away. “We can make a dramatic impact in reducing mortality through early detection,” says Joshua Ofman, chief medical officer and external affairs. “Our test was designed to detect any cancer and where in the body it’s located with a single blood draw,” he says. “Our goal was a false-positive rate of less than 1 percent, and we’ve surpassed that.” The company is using a technology that looks at methylation—or how genes are expressed—combined with machine-learning algorithms to classify cancer signals from non-cancer ones. The company plans to return recent study results to physicians and patients later this year.

In the meantime, liquid biopsies are already becoming part of mainstream medicine for advanced cancer patients. “A lot of cancer patients don’t know there’s another way to follow their course of cancer. Instead of undergoing an organ biopsy or MRI or CAT scan, you can give a tube of blood,” Topol says. “Which would you rather do?”