He watched his brother die from a cancer that no drug could cure. Globally, eight million people died of cancer in 2012. Now one of the world’s most renowned cancer researchers says it’s time for Plan B. The answers Bert Vogelstein needed and feared were in the blood sample.
Vogelstein is among the most highly cited scientists in the world. He was described, in the 1980s, as having broken into “the cockpit of cancer” after he and coworkers at Johns Hopkins University showed for the first time exactly how a series of DNA mutations, adding up silently over decades, turn cells cancerous. Damaged DNA, he helped prove, is the cause of cancer.
Now imagine you could see these mutations—see cancer itself—in a vial of blood. Nearly every type of cancer sheds DNA into the bloodstream, and Vogelstein’s laboratory at Johns Hopkins has developed a technique, called a “liquid biopsy,” that can find the telltale genetic material.
The technology is made possible by instruments that speedily sequence DNA in a blood sample so researchers can spot tumor DNA even when it’s present in trace amounts. The Hopkins scientists, working alongside doctors who treat patients in Baltimore’s largest oncology center, have now studied blood from more than a thousand people. They say liquid biopsies can find cancer long before symptoms of the disease arise.
This particular blood sample, though, was personal. It was from Vogelstein’s brother, an orthopedic surgeon one year younger. He was fighting skin cancer, and the disease was already spreading. There was hope he’d respond to a new type of drug, but the treatment causes swelling, and it’s difficult to tell from an x-ray or CT scan whether the cancer is melting away or not. So Vogelstein used his lab’s new technology. If the cancer DNA had disappeared from the blood, they might celebrate. If it was still there, maybe he could steer his brother to some last-ditch drug.
“We tried to guide the treatment. That was the hope, anyway,” says Vogelstein. His voice tightens. He doesn’t say what happened next.
The obituary of Barry Vogelstein, born in Baltimore, appeared on July 3, 2013.
We’re not winning the war on cancer, and the death of Vogelstein’s brother shows why. Too many cancers are caught when they have become incurable. Each year, $91 billion is spent on cancer drugs worldwide, but most of those medicines are given to patients when it’s too late. The newest treatments, created at staggering expense, cost $10,000 a month and often extend life by only a few weeks. Pharmaceutical firms develop and test more drugs for late-stage cancer than for any other kind of disease.
“We as the public and as scientists have been entranced by this idea of curing advanced cancers,” says Vogelstein. “That is society’s Plan A. I don’t think that has to be the case.” There are other ways to reduce cancer deaths: wearing sunscreen, not smoking, and getting screened to catch cancer early. To Vogelstein, all these preventive steps represent “Plan B” because they receive so much less attention and funding. Yet when prevention works, it has better results than any drug. In the United States, the chance of dying from colorectal cancer is 40 percent lower than it was in 1975, a decrease mostly due to colonoscopy screening. Melanoma skin cancer, too, is treatable with surgery if caught early. “We think Plan B needs to be Plan A,” says Vogelstein.
The new blood tests could make that possible. For the first time, Hopkins researchers say, they are within reach of a general screening tool that could be used to scan broadly—perhaps at an annual physical—for molecular traces of cancer in people with no symptoms. “We think we’ve solved early detection,” says Victor Velculescu, a Hopkins researcher who runs a lab in the building next to Vogelstein’s.
Making such screening a routine practice in medicine will be challenging. One difficulty is that while the test may detect the presence of cancer DNA in the body, physicians might not know where the tumor is, how dangerous it is, or even whether it is worth treating. “We have to be cautious about how we talk about that,” says Daniel Haber, director of the Massachusetts General Hospital Cancer Center. He believes the DNA blood tests are “far from ready” and says very large studies will be needed to prove that they are useful. “There is a huge bar to get over,” he says.
Despite such skepticism, the technology is gaining attention. Tony Dickherber, head of the Innovative Molecular Analysis Technologies Program at the National Cancer Institute, says the idea of scanning blood for tumor DNA was “fringe at best” only three years ago. But now labs and companies from California to London are jumping in, producing a stream of improvements to the blood screening technology and new data supporting it. “People are starting to think that Vogelstein is right—this could be the best way to do early diagnosis,” he says. “[It] could be done much more widely than other screening technology we have, and you could screen for an incredible range of cancers.”