Mayo Clinc scientists on the trail of a 'pan cancer' test

Mayo Clinic is in a race against itself on a project that could revolutionize cancer care, as two research teams pursue a "pan cancer" test that could detect the presence and severity of multiple types of the disease.

On one side is Dr. David Ahlquist in Rochester and his partnership with Exact Sciences, which together already produced a home test for colon cancer known as Cologuard.

On the other is Dr. Keith Stewart in Scottsdale, Ariz., and a Mayo partnership with Grail, a start-up company with the financial backing of Bill Gates and Jeff Bezos, which launched a large breast cancer screening trial this month.

Both teams believe that a simple blood draw and analysis could soon produce a way to screen for a dozen types of cancer. Both are taking advantage of improved understanding of human genetics and cancer tumors, and technological advances that track genetic activities that were once beyond detection.

"There's been a convergence of advances that allows us to re-imagine how screening itself is done," said Ahlquist, a Mayo gastroenterologist who coinvented Cologuard, a stool-test kit consumers can use at home. "We have the analytical sensitivity now with tools to detect down to the really tiny amounts of DNA or other markers that are present in blood to detect even early-stage cancers."

Cancer is the second leading cause of death in the United States, claiming a half-million lives each year. Development of a pan test could be a breakthrough, because most types of cancer aren't identifiable until they have grown and produced symptoms, and because existing cancer screenings are somewhat problematic.

Experts differ, for example, on when to use mammograms for breast cancer in women and how to interpret PSA tests for prostate cancer in men. And while CT scans find most lung cancers in smokers, they also produce false positives that scare healthy people into thinking they are sick.

The underpinning of Stewart's work is the discovery in the past decade that cancer tumors shed DNA into the bloodstream — potentially creating signatures by which they can be identified without imaging scans or even surgical biopsies.

The Grail trial will examine blood from 120,000 women seeking scheduled mammograms at Mayo facilities in Minnesota and Wisconsin, and at Sutter clinics in California. Over time, researchers hope to detect reliable distinctions in the blood of women with breast cancer that will make screening possible without the discomfort and slight radiation exposure of mammograms.

"It's like sending one of those submersibles" into the ocean, Stewart said of the DNA research. "We don't know what's down there. It's kind of like unexplored territory."

While the goal is a single test for multiple cancers, it will probably come through development of accurate blood tests for individual cancers first, the Mayo researchers said.

Ahlquist is nonetheless on his way to establishing potential blood markers for numerous cancers. In results presented this month at a conference of the American Association for Cancer Research, Ahlquist and colleagues showed that four markers in blood could predict 96 percent of lung cancers.

The false positive rate — in which the marker tests suggested cancer in healthy people — was 6 percent. Ahlquist said that is lower than the 25 percent false positive rate for lung cancer CT scans (although some studies suggest the scans are far more accurate than that).

The marker study was limited in that it reviewed fewer than 400 samples from a research blood bank, but Ahlquist said it showed promise, including the accurate detection of cancers at both early and late stages.

"You have to detect those early stages," Ahlquist said. "If the test only detects [cancer] in advanced stages, it's not really helping."

Ahlquist's research is focused on methylation, the activation of human genes that differentiates parts of the body, but also forms tumors.

"We have a way now to decode the methylation pattern," he said.

Mayo officials said the two research projects aren't rivals, and should complement one another. Nor is it uncommon for Mayo colleagues to work with competing companies on similar aims; radiologists, for example, have worked with competitors Phillips and GE on imaging technologies.

A key for both projects is not just identifying cancers, but separating those that need treatment from those that can be left alone. Stewart said it's possible that blood tests could raise alarms about tiny tumors that the immune system can kill off on its own.

"Maybe then you just cause anxiety," he said, "where there's really no need."

The ability to differentiate cancers by severity could determine whether blood tests are one day used to follow cancer patients after treatment, to check high-risk patients for disease, or to screen the entire population regardless of individual risk. Ahlquist said it is important to differentiate this research from existing blood tests for genetic or family risk.

"This is not measuring DNA to forecast cancer risk," he said. "This is a test that indicates the presence of a cancer."

Jeremy Olson • 612-673-7744