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Gallery: Breast cancer research at OHSU
Joe Gray hopes to unlock the secrets of breast cancer.
His work could pave the way for the development of powerful new therapies that target individual tumors, vastly improving and saving lives.
It's an ambitious undertaking, but that's what Gray does. In the 30 years that he's focused on breast cancer, he's helped develop technologies that have thrust the field forward and cut mortality rates.
His latest project, still in the planning stages, will enlist breast and other cancer patients in the Portland area in a clinical trial.
Gray, a scientist at Oregon Health & Science University, is devising a trial unlike most others. His team, including the trial's leader, Dr. Raymond Bergan, will give participants cancer drugs and then biopsy their tumors as the trial progresses to check the results.
If the drugs don't work, the scientists will try something else. The idea is to come up with an optimum treatment for each patient.
"This is absolutely going to teach us as researchers and clinicians collectively how to do a better job of treating the individual patient," Gray said. "This is the essence of precision medicine."
Gray started his career as a nuclear physicist at Lawrence Livermore National Laboratory in California in the early 1970s. After nearly two decades, he moved to the University of California at San Francisco, and became directly involved in breast cancer research. His interest in working on cancer stems from his family. His father died of lung cancer at 64 when Gray was 28.
Five years ago, he moved to OHSU, where he's continued his research. The university considers Gray quite a catch. He's one of the top researchers in his field.
"It's staggering the impact he's had on cancer," said Colin Collins, a former collaborator who is director of the Laboratory for Advanced Genome Analysis at the Vancouver Prostate Centre in British Columbia.
Tall and trim, Gray looks like a scientist with his short-cropped gray hair, wire-rimmed glasses and pin-stripped shirt. He peppers his speech with words like "whilst" but has a friendly, inviting grin. Although 70, he looks a decade younger and still has lofty goals to accomplish.
Gray's inventions have helped scientists sharpen the diagnosis of cancer, for the breast in particular, and to analyze the range of abnormalities in tumors. His goal now is to find ways to distinguish between lethal and non-lethal tumors and to be able to understand how cancer cells evolve so doctors can attack them with the appropriate drug.
He's already achieved that for a type of breast cancer that affects about 15 percent of patients. Using his technology, scientists can determine who will benefit from the drug Herceptin. The mortality rate of those patients has dropped by 60 percent thanks in part to Gray's work, said Paul Spellman, professor of molecular and medical genetics at OHSU.
Gray and Bergan plan to start the clinical trial at OHSU in January. They aim to personalize cancer treatment and understand why some drugs don't work.
Hundreds of drugs are being developed for cancer, including about 100 for breast cancer alone, Gray said. Before they're approved and marketed, they have to be tested in a clinical trial.
Most trials test one drug and pose one question, Gray said: Does it work?
"Ninety-five percent of the time they don't work as expected," Gray said.
He wants to learn from those failures as they happen to pave the way for effective therapies.
OHSU will recruit about 50 people for the trial. All must have a late stage form of either acute myeloid lymphoma, a blood cancer or breast, prostate or pancreas cancer that has spread to other parts of the body.
They also must have gone through the standard of care in terms of treatment, essentially reaching the end of the line.
"This is the program I would want to be on if I had metastatic cancer," Gray said.
The trial will be one of the few to take biopsies of patients while treating them.
Another trial, at the University of California at San Francisco where Gray used to work, involves scientists taking biopsies of breast cancer patients during treatment. The scientists haven't been able to analyze the tissue quickly enough to use that information to select new treatment.
Gray, however, has a secret weapon: a laboratory of custom-built, high-precision microscopes. They sit in the basement of OHSU's Collaborative Life Sciences Building on the South Waterfront, surrounded by an underground moat. That eliminates vibrations from the building, which would make it impossible to snap pictures unveiling the inner machinery of a tumor.
"Joe is working with the highest imaging technologies that are available in the world today," Spellman said.
The microscopes enable his team to create hand-sized mockups of tumor cells. Each cancer is made up of proteins, formed into cells, formed into sub-tumors, formed into a mass. Understanding how the tissue works requires understanding how it is organized at various levels.
The study will involve a multidisciplinary group, one of Gray's hallmarks.
"If we want to capitalize on the incredible new information that we are able to generate, we need to have teams of people who will work together," said Dr. Gordon Mills, chair of the Systems Biology department at the University of Texas MD Anderson Cancer Center in Houston. "He's the ultimate collaborator and colleague to work with."
Gray plans to start taking biopsies of cancer patients this month to test his lab's ability to analyze the tissue quickly. The project has to be approved by the university's ethics board before it can start.
It is expected to last two years. If all goes well, it could be expanded. The information that emerges will likely add more pieces to Gray's overarching goal to put together a Google Earth-style holistic view of cancer.
-- Lynne Terry