A lifelong search for answers

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Cancer
October 29, 2019
Jane and Joe Gray

Joe and Jane Gray know cancer well. For over 40 years, their lives have been shaped by this disease. But, along the way, they have also transformed how we treat it. Today, Jane helps scientists test revolutionary new treatments. And Joe continues his lifelong search for answers.  

Joe has been paving the way in breast cancer research for the past 30 years, inventing technologies that hone diagnosis and cut mortality rates. As a physicist and researcher, he spent more than four decades leading his field in genomics, cancer genetics and breast oncology at three top institutions, Lawrence Livermore National Laboratory, the University of California at San Francisco, and the Lawrence Berkeley National Laboratory until he came to OHSU in 2011. Today, he’s homed in on what could be his greatest life’s work — precision oncology, the ability to target individual cancers with personalized treatments.

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Despite his impressive achievements, Joe has a humble way about him with a gift for translating complex science into intuitive metaphors. With kind eyes and an approachable grin, his innate calmness easily morphs into admiration when his wife is in the room. 

“We’ve been married 52-and-a half years,” Jane said with a teasing smile. “But he has an 88-year contract.” 

Jane has always been the bedrock of the family, managing the home and raising their son while Joe spent hours in the lab or on the road. And she is still his biggest advocate. “He has always had this passion,” she said. “And I’ve always believed in it.”

Joe’s abiding devotion to his wife and his family helps drive his career. At 24, he watched his father die of lung cancer, witnessing first-hand the ravages of the disease and the grief it leaves behind. Then, 40 years later, cancer struck again. This time, it was his wife.

Joe was traveling when Jane called to relay the news, and Joe wasted no time contacting surgeons and researching treatment options. “The next thing I know, he’s home,” Jane said. 

The following day, she sat on the couch in their living room, while Joe and one of his colleagues discussed her future. She remembers her head bobbing back and forth, as she watched them review the literature, perform a risk analysis and debate treatment options. “Finally, I asked, ‘I’m having chemo, aren’t I?’” she said. “And that’s when I cried.”

For Joe, that day marked a turning point in his career. “That was the start of my thinking about personalization of medicine. Up until that moment, it had been an academic exercise. But in the living room that day, we were assessing all of the data and trying to determine what we were going to do about this individual cancer. It made our whole research enterprise over the last 30 years much more personal,” he said.

Jane’s treatment in 2010 was initially a success. She thought she was in the clear until one chilly day in February 2017 when she learned that her cancer had returned. This time, it had metastasized and traveled through her bloodstream, creating multiple tumors throughout her body. The five-year survival rate for her type of stage four metastatic breast cancer is 22 percent.

“I was in denial,” she said. “I only had a three percent chance of recurrence. Three percent.”

It just so happened that Jane’s aggressive form of cancer was a perfect match for a clinical trial Joe and his colleagures were about to launch at the OHSU Knight Cancer Institute. A circumstance that turned her husband’s work into her best chance of survival.

Within a few days, Jane became one of the first 50 patients in SMMART, a clinical trial to test a life-saving new approach to treat this very disease.

A SMMART approach to treating cancer

SMMART was an idea born during Joe’s tenure at UCSF. “While I was there, I learned two important things: every cancer is different, and cancers evolve over time,” he said. 

The standard of care for cancer usually employs a combination of treatments. After a period of time, imaging is done to determine the treatment’s effectiveness. 

“By then it may be too late,” Joe said. The cancer can adapt and become drug-resistant. But what if doctors could make regular analyses during treatment that would indicate how the cancer had evolved? At the time, there were new technologies becoming available that could analyze the inner workings of evolving tumors. At the same time, hundreds of cancer drugs were being developed in clinical trials, but most of these trials only tested one drug in a cohort of patients, rather than a combination of drugs in an individual patient.

So, Joe posed the question: What if we use our best available diagnostics and our best combination of drugs to pick the best treatment for each individual? He wrote a grant proposal to test his idea. The person reviewing his grant was none other than Brian Druker, MD, director of OHSU’s Knight Cancer Institute and the JELD-WEN Chair of Leukemia Research. Druker was impressed, and invited Joe to look into OHSU. 

After many conversations, the Grays made the move to Oregon where Joe now holds positions as Professor and Gordon Moore Endowed Chair of the Biomedical Engineering Department; director, Center for Spatial Systems Biomedicine; and associate director for biophysical oncology at the Knight Cancer Institute. Soon after their move, Joe began his work on SMMART, also known as Serial Measurements of Molecular and Architectural Responses to Therapy. 

Today, SMMART is led by Dr. Gray, Gordon Mills, MD, PhD, director of precision oncology at the OHSU Knight Cancer Institute and the Wayne and Julie Drinkward Endowed Chair in Precision Oncology, and Christopher Corless, MD, PhD, executive director and chief medical officer of the OHSU Knight Diagnostic Laboratories, and supported by Zahi Mitri, MD, assistant professor of medicine at OHSU, as well as a team of over 150 dedicated individuals throughout multiple disciplines. 

As part of the trials, doctors use a combination of targeted therapy drugs to stop tumors before they can adapt and become drug-resistant. This scrupulous approach blocks cancer cells with minimal disruption of healthy cells and tissues. The very nature of the trials is to find the best possible treatment in real time and that requires a certain degree of adaptability for both doctors and patients. It also calls for a willingness to try new things.

“I’m fortunate I’m alive. If my husband had taken a different path, I wouldn’t be here today,” Jane said.  

Jane knows this all too well. As part of SMMART, she is often subjected to a lot of poking and probing, testing and retesting. “Sometimes you just get tired,” she said. “Tired of the unknown.”

Despite the exhaustion, Janes finds the strength to forge ahead, and she is an invaluable participant. 

“She is teaching us how to manage a patient with advanced cancer,” Joe said. “With her participation in SMMART, she is providing critical insight that could help thousands of patients in the future.”

Cancer treatment is usually determined by the maximum tolerated dose, or the highest dose of a drug or treatment that does not cause unacceptable side effects. However, not everyone can endure this high dosage. 

Take, for example, rashes: one of the listed side effects of some treatments. On paper, a rash might not seem like a deal breaker. But Joe witnessed firsthand that rashes made his wife miserable. They affect her quality of life and, therefore, can be therapy limiting.

“Turns out, it’s a really big deal,” Joe said. 

“In SMMART, we try to figure out how little we can give rather than how much the patient can tolerate,” Joe said. It’s this unique approach that forms the foundation of the SMMART motto: Durable and tolerable control of the cancer.

“There’s actually an interesting field of study in ecology,” Joe said. “How do you manage weeds in your field? You don’t burn the field down in order to get rid of the weeds. You treat the field enough to keep them down. If you gave enough pesticide to kill all of the weeds, you’d probably kill all of the wheat. So what we’re trying to do is to keep the weeds down.”

Durable and tolerable. And effective.

So far, it’s working. In early results, over half of participants responded exceptionally well to treatment, well beyond the 30 percent response rate the team hoped to achieve and roughly double the response rate achieved in studies using single drugs. 

And Jane’s cancer? It’s nearly gone, except for three tiny lesions.

“I’m fortunate I’m alive. If my husband had taken a different path, I wouldn’t be here today,” Jane said. 

The critical role of philanthropy

Joe’s long-term vision is to make sure everybody has this possibility. “I want to demonstrate on a broad scale that SMMART dramatically improves our ability to tolerably and durably treat cancer and to see it spun out into the world. That’s why I’m still working here in the lab.”

Once proved successful, the next big question is: How do you make SMMART available to everyone?

Researchers cannot depend on government funding in a highly competitive environment where many worthy projects are competing for dwindling federal dollars. There simply isn’t enough to go around. In fact, Joe recently calculated that average researchers spend over half of their time writing grants that don’t receive financial support. 

“Public funds,” says Gray, “generally support steady advances in science that are clearly moving us forward. That’s important, but if you want to break new ground and do truly ambitious work like SMMART, we’re going to have to rely on philanthropy.”  

Private donations have mostly financed SMMART so far. The Grays themselves have donated generously over the years, including establishing a professorship.  But the need continues to grow.

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“We've been blessed with great support,” Joe said. “But the treatments Jane and other SMMART patients get are complicated to manage and some of the drugs are used off label. We need philanthropy to fund this work.”

As for Jane, her vision is crystal clear. “I just want a few more years,” she said with a smile and squeezed Joe’s hand. “I don’t want to be selfish, but maybe I’ll ask for 10.”

Category: Cancer

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