Brain-cancer center at Swedish maps tumors to design treatment

There's never a good time to have brain cancer.

Still, Karl DuBose tries to look on the bright side.

"It's weird to say, but today — and here in Seattle — might be the best time and place to get this disease," said the 45-year-old Everett man, who was slammed with the diagnosis last summer.

Long neglected by researchers and drug companies, brain cancer now is being targeted in clinical trials of nearly 15 new medications. Genetic technology is enabling personalized treatment on a level never before possible. And though the disease remains the most malignant form of cancer, some doctors say it's time to stop treating it like a death sentence.

Seattle's only nationally recognized brain-cancer program is at Seattle Children's, so the city seems an unlikely place for those trends to converge. But a pianist-turned-neurosurgeon at Swedish Medical Center is on a mission to boost the city's standing by tapping into the science for which Seattle is renowned.

"We're sitting in one of the great technology centers of the world," Dr. Greg Foltz said. "Why not use that to advance the treatment of this devastating disease?"

Foltz was playing piano for the St. Louis opera and headed for The Juilliard School 14 years ago when a friend's daughter died of brain cancer. Stunned to learn how little could be done for patients at that time, he gave up music for medical school.

Now, as head of the new Center for Advanced Brain Tumor Treatment at Swedish, Foltz, 45, has forged a coalition with local research centers and biotech firms. They apply cutting-edge tools to the treatment of patients and work toward better ways to fight the disease.

"Greg has really transformed the whole research landscape in Seattle around brain cancer," said Dr. Leroy Hood, leader of the Institute for Systems Biology and a pioneer of genetic sequencing. Working together, Hood and Foltz are pushing the frontiers of personalized medicine, by tailoring brain-cancer treatments for individual patients.

Foltz and his colleagues genetically map each tumor they remove or biopsy, examining 30,000 genes to determine which are switched off or on. The pattern can reveal genetic glitches responsible for a specific cancer's runaway growth. Such mapping is done at major brain-cancer centers for select patients such as Sen. Edward Kennedy, D-Mass., recently diagnosed with brain cancer.

Foltz does it for every patient, free of charge.

"This is a unique fingerprint," he said, heading to his lab after a two-hour surgery to tease a walnut-size growth from deep inside a woman's head. "The tumor I just removed is already being analyzed."

Foltz also works with Microsoft co-founder Paul Allen's Allen Brain Institute, which has assembled genetic maps of healthy brain tissue that provide valuable comparisons.

Armed with genetic insight into what makes a patient's tumor tick, Foltz and his team often can predict how aggressive the cancer is and how it will respond to certain chemotherapy drugs. "If I think a tumor is going to behave more aggressively, I can watch it much more closely, do more frequent MRI scans and quickly switch to a different chemo drug at the first evidence of tumor growth," he said.

Using this approach, Foltz said he believes he's been able to extend some patients' lives by up to a year. He's launching a clinical trial to see whether data will support that conclusion.

"Wave of the future"

Scientists at the University of California, San Francisco (UCSF) and other research centers are doing similar research on what makes some tumors more aggressive, but few have taken the more experimental step of using genetic tumor maps to design treatments, Dr. Mitchel Berger said.

"This is the ultimate example of what we want to achieve in the future — namely personalized medicine," said Berger, head of neurosurgery at UCSF, the West Coast's leading brain-cancer center. "Greg is doing some very innovative ... work."

DuBose is hopeful his individually tailored treatment plan, which has included two surgeries, radiation and three types of chemotherapy, will help him buck what are bleak odds.

About 22,000 Americans — 1,200 in the Northwest — are diagnosed with malignant brain or spinal-cord tumors annually. Few will survive more than one to three years. DuBose's cancer is the most common and aggressive type: glioblastoma multiforme, described as incurable by many experts.

DuBose, who runs a carpet-cleaning business, was playing with his dog when he suffered a seizure and wound up in the hospital. Scans revealed a tumor the size of a pingpong ball behind his right temple. Local doctors offered little hope.

"They pretty much wrote me off," DuBose said.

That fatalistic attitude doesn't sit well with Dr. Henry Friedman, a noted brain-cancer expert at Duke University Medical Center. He noted in an essay last year that a small, but growing, number of people seem to survive glioblastoma. He urged fellow doctors to be more aggressive in treating the disease.

Several of his patients are healthy 11 years after being diagnosed, Friedman said. "Ten years ago, you wouldn't see anything like that."

Because it's rare and can kill quickly, brain cancer has been an orphan disease with limited appeal to researchers. Only two new treatments have been approved in the past 25 years.

But advances in biotechnology have led to more than a dozen new drugs now being tested, including Avastin, or bevacizumab, which dries up tumors' blood supply and has proved partially effective against other cancers. An experimental vaccine more than doubled survival times for a small group of patients with a particular variant of glioblastoma multiforme.

"Now we understand this disease much better than we ever have, and that gives us a whole new group of targets to go after," Berger said.

More and better treatments likely will come out of the work of Foltz and other scientists to sort out the genetic and molecular blueprints of individual tumors, Friedman said. "That is the wave of the future."

Surgeon, scientist, entrepreneur

Researchers recently sequenced the genes from glioblastoma cells, identifying new mutations linked with the disease. Foltz and his colleagues are mining data from frozen bits of more than 300 tumors, searching for patterns that predict outcomes and vulnerabilities that might be exploited to attack the disease.

They're also using a $1 million cell sorter to isolate so-called cancer stem cells. These mysterious cells account for only about 1 to 5 percent of most cancerous tumors, but some scientists believe they are the cells most responsible for malignant growth.

"We're trying to figure out why these tumors grow back." Foltz said.

An unusual combination of surgeon and scientist, Foltz also has the spirit of an entrepreneur. He helped hustle up $3 million in donations for the Swedish brain center, which opened last month. He lured one of Hood's top scientists away to join him. Foltz's average day starts with predawn piano practice, then moves on to several surgeries, hours in the lab and phone conversations with patients — all of whom get his cell number.

His latest collaboration, with Accium Biosciences, is the product of persistence. The company, which works mainly for drugmakers, wasn't enthusiastic when Foltz first tried to enlist it in the brain-cancer cause. But he kept looking for an angle and found it — along with an $850,000 federal grant.

The team now is using Accium's 15-ton particle accelerator to analyze tumor tissue and figure out how much of a specific drug reaches its target. In addition to being useful for drug development, the information can improve patients' care by identifying medications that aren't working well.

Foltz tries to spend one day every week spreading the word about brain cancer and the need for more study, and those efforts led to a new collaboration with the Sammamish-based Chris Elliott Fund. Founded by Dellann Elliott after her husband died of glioblastoma in 2002, the foundation has raised nearly $1 million in grants and donations for research. Now, Elliott is working with Foltz to reach out to the half of brain-cancer patients in the region who never come to a major medical center for treatment.

"We feel it's so important for these patients to know they have the option of having their brain tumor profiled, and that there are many treatment options out there," she said.

It's been more than a year since DuBose's diagnosis. Except for a slight blurring of his vision, his ordeal hasn't taken much of a physical toll. "I'm still working. I can do pretty much anything I want," he said. But the disease has been all-consuming for him and his family.

"I've kind of let this take over for the last year," DuBose said. "I'm going to fight this tooth and nail, but I also realize I need to get on with my life."

Sandi Doughton: 206-464-2491 or sdoughton@seattletimes.com

The information in this article, originally published Nov. 25, 2008, was corrected Nov. 25, 2008 and Dec. 4, 2008. The Chris Elliott Fund is based in Sammamish, Wash. A previous version of this story incorrectly reported that the fund was based in Snohomish, Wash. A previous version of this story also reported that Seattle has "no nationally-recognized brain cancer program." But the pediatric brain cancer program at Seattle Children's Hospital, which involves faculty at the University of Washington, is a member of the Pediatric Brain Tumor Consortium. The consortium includes the top institutions in the field of research on brain cancers that afflict children. The University of Washington has also received $10 million in federal and foundation funding for brain cancer research, and, with the Fred Hutchinson Cancer Research Center, is a National Cancer Institute-designated neuro-oncology research center.