September 08, 2015

Kelsey's Story: Discovering New Hope for Childhood Cancer at The Jackson Laboratory

A faster way to fight cancer

The story of Kelsey Gallagher highlights the hope and the limitations of current therapies for cancer. The future of cancer treatment lies in more personalized, precise medicine, fueled by the latest scientific advances. The Jackson Laboratory is using genomics and cancer avatars to identify, faster and with greater precision, which treatments will be effective in the individual patient.

Toward the end of her young life, Kelsey Gallagher told no one she had advanced cancer. As much as possible, she wanted a normal teenager’s life, not the sympathetic persona of a victim.

While taking palliative chemotherapy, she went to her high school prom, performed a leading role in a play, took classes at a community college, spent hours in the photography darkroom, practiced piano, painted, sculpted, made jewelry and even played three sets of tennis with a collapsed lung just weeks before she died in 2005, a month shy of her 18th birthday.

“She went off that cliff at 100 miles per hour,” recalls her father, Sean Gallagher, a software executive from Newtown, Pa., and a supporter of The Jackson Laboratory. “She was very active until the very end. We are still in awe. She was a student and artist – not a victim. There was never a complaint – only her mantra, ‘I feel good today; what do you want to do?’” 

From the time she was diagnosed with Ewing’s sarcoma, a rare bone cancer, at age 11 as a sixth grader, Kelsey and her parents and three siblings endured an extreme physical and emotional ordeal in and out of the cancer ward at Children’s Hospital of Philadelphia.  

First there were several cycles of chemotherapy to shrink a tumor in Kelsey’s leg, accompanied by hair loss, nausea, mouth sores and other brutal side effects. Then came a six-hour surgery to remove the remaining tumor from her fibula.

“At that point we thought we were in pretty good shape, Gallagher remembers. “We were pretty sure she was cancer free.”

Even so, routine blood tests revealed the onset of leukemia, a secondary cancer likely caused by the chemotherapy treatments for the Ewing’s sarcoma. The leukemia required more harrowing medical treatments – total body irradiation, followed by a bone marrow transplant using marrow donated by her older sister, Thea.

Kelsey had a friend in the cancer ward whose Ewing’s sarcoma prognosis was much worse than her own, because the cancer had spread to the ribs, where it was inoperable. “You just say, ‘This kid isn’t going to make it,’” Gallagher says. But that friend today is in complete remission as an adult, while Kelsey’s cancer later recurred in her lungs and proved fatal.

“I guess what it shows you is that these treatments are guesswork in a certain way, “Gallagher says. “At the end of the day whatever we tried didn’t work, and we didn’t have the time to figure out what would work.” 

Gallagher was baffled by how two patients with the same cancer diagnosis and treatment could have such drastically different outcomes.

He has since learned it’s because every person is genetically different, and so is their cancer. A treatment that works for one won’t necessarily work for another.

Precision medicine with cancer avatars

“The historical approach to treating cancer is kind of a one-size-fits-all treatment, a treatment approach that’s no different from one cancer patient to the next,” says Jackson Associate Professor Kevin Mills, Ph.D., who researches cancer. “Now that we’re in the genome era, we can begin to think about a different way of treating cancer.”

One novel approach to finding the right therapies for each patient’s specific cancer is under way at The Jackson Laboratory.  It relies on a special JAX mouse with an altered immune system that can tolerate implanted human tumors.

“That mouse becomes your surrogate, your avatar, in the experimental space,” says cancer researcher Edison Liu, M.D., Jackson’s president and CEO.

A small piece of solid tumor is taken from a patient and transplanted into one mouse. As it grows, the tumor is subdivided and implanted into five more mice, and so on.

“It’s almost like a photocopying process where you have many mice now all carrying a tumor from an individual patient,” explains Professor Carol Bult, Ph.D., scientific director of the cancer avatar program. “And you start treating those mice as if they were the patient.”

Various drugs and drug combinations are tested in the mice to see which ones work and which ones don’t.

“And you say, aha, treatment A works, treatment B doesn’t work. And you do that testing in the tumor-bearing mice instead of on the patient,” Bult says.

Unlike with patients, who receive treatments sequentially over long periods, multiple experiments can be done simultaneously in mouse avatars, accelerating the identification of effective treatment options.

“So now we have the ability to actually test new ideas and new drugs in a matter of months, not in a matter of years,” says Susie Airhart, senior director of strategic opportunities and product development.

Avatar experiments are also enabling researchers to correlate cancers to precise genetic sequences and mutations in the human genome.

“We’re going to take all of the information we get, not just for one patient but for tens of thousands of patients, and we’re going to put all of that information into a database,” Bult explains. “And eventually we’ll have such a rich knowledge base that we won’t have to use those mice anymore. You put in the DNA sequence, and a doctor will get back a report that says patients with this DNA sequence pattern responded best to these treatments. That would be cheap enough and easy enough to apply virtually anywhere.”

“That’s where personalized medicine is going,” Gallagher says. “It’s to understand what works, why, and how we can be more precise, more exact, and minimize the difficulty that we sometimes put these children through.   So next time, maybe if a Kelsey comes in the hospital, they’ll say, ‘Oh, you’re different than the last Kelsey and we’ll give you this particular protocol because of your immune system, because of the way that your genes are, the way that the cancer’s expressing itself.’”

Gallagher learned about the cancer avatar program during a chance meeting with Ed Liu a few years ago in Bar Harbor, Maine, where his family has a summer home.

“That’s exactly what Kelsey could have used,” he remembers telling Liu. “That kind of research is exactly the type of work that will lead to cures for children like Kelsey.” 

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