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New gift broadens reach of Rady’s genetics institute

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A new $10 million gift to support neuro-oncology research at Rady Children’s Hospital San Diego focuses on opening more avenues of treatment for kids like 3-year-old Gemma Guion.

Already, a genetic test has added precision to doctors’ efforts to shrink the slow-growing tumor on Gemma’s brain stem. But more can be done to connect the frontline neuro-oncologists at Rady to the geneticists, computer scientists and other specialists exploring the leading edge of a “precision medicine” revolution that seems to turn up important new findings with each passing day.

“This grant gives us the opportunity to bring these different types of expertise together, and that’s very, very exciting,” said Dr. Stephen Kingsmore, director of Rady’s genetics institute.

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The center was formed in 2014 with a $120 million donation from La Jolla philanthropists Ernest and Evelyn Rady. The plan was to concentrate first on children in the hospital’s intensive-care units suffering from undiagnosed, life-threatening conditions.

Sequencing the genomes of these patients has the potential to spot rare mutations that can quickly hint at novel, more effective treatment options. Kingsmore was in the thick of building a team to accomplish this initial mission when the $10 million donation arose, prompting the institute to add cancer to its growing list of targets.

It’s a big addition because cancer is often driven by a whole basket of mutations, Kingsmore said. Determining which DNA changes are actually responsible for malignancy, and which are simply red herrings, can be much more complex than diagnosing the single-gene mutations that tend to cause the rarer pediatric diseases.

“The beautiful thing is, this gift switches on a new program for us a lot earlier than I had anticipated,” Kingsmore said.

The contribution — third largest in the hospital’s history — comes from the Joseph Clayes III Charitable Trust, whose namesake was a successful Southern California real estate investor, avocado rancher and philanthropist dedicated to endeavors ranging from the arts to children.

Co-trustee and niece Trulette Clayes said she is sure that her uncle Joe, who died in 2007, would have loved the investment in Rady’s.

“He’d be honored, proud and he’d probably be driving them all crazy cause he’d want to know what’s going on. Every single day, he would be so excited about it. He was very inquisitive,” Clayes said.

The donation, which comes after the foundation’s $3.5 million contribution to Ronald McDonald House Charities of San Diego in 2013, starts to fulfill Ernest Rady’s hope, expressed in 2014, that his kick-starter gift would spur others to contribute as well. Clayes said she has similar intentions.

“I hope this gift inspires others to give to this cause. I will be involved as much as I can to get the word out so that other people contribute,” Clayes said.

Seeing her uncle’s largesse used to explore this new frontier of genetics is just plain exciting, she added.

“We know we are going to change the world,” she said.

Such changes are happening at Rady and many other hospitals across the world as clinicians begin to use new genetic tools increasingly at their disposal.

Gemma’s case is a good example of what’s possible and what remains to be done.

When physicians found Gemma’s tumor just after her second birthday, its finger-like projections were pressing ever more insistently on the nerves that control her body’s most basic functions — swallowing, balance, breathing, hearing. A first round of chemotherapy failed to shrink the tumor, and Gemma struggled to walk.

When it was time to try something else, Dr. John Crawford, a neurologist at Rady, opted to biopsy the tumor even though it is in a very sensitive spot that’s prone to collateral damage. Surgeons took a tiny tissue sample and sent it off for testing. The results came back positive for a mutation in the BRAF gene that can cause the out-of-control cell division that builds tumors.

Spotting the mutation qualifies Gemma for a clinical trial that could deliver significant gains. And having that clear target is a gift for her parents, Teal and Patrick Guion of Oceanside.

“There are a million different types of chemotherapy to try when you have a glioma (tumor) like this. But this is my kid. She’s only 3. I don’t want to try a bunch of chemos on her that might work. I want to try the one that they can show is probably going to work the best for what her tumor is made of,” Teal Guion said.

However, the clinical trial is not quite ready to start yet.

In the meantime, Crawford needed to find something to beat back the tumor’s growth. He decided to put Gemma on Avastin, a cancer drug that works well in fighting colon and lung cancers but has mixed results against brain tumors like hers.

Avastin, it turned out, was just the trick. Weekly infusions of the medication have caused the tumor to shrink by half.

“This is the best response I’ve ever had with this particular drug,” Crawford said.

But the result begs a question: Why?

Why did Gemma’s tumor respond so well to Avastin while others haven’t? Crawford suspects her mutation may hold the answer.

“Maybe the genetic information is a surrogate for the responsiveness to this drug? Maybe this mutation causes it to respond to Avastin,” he mused.

This is where the Clayes’ $10 million donation comes in. It will be used to create a research fund, an endowed chair in neuro-oncology and annual fellowship stipends for bright young minds entering the field to come to Rady and explore the possibilities. Kingsmore said this infrastructure, on top of the institute’s broader base of work, should help clear up more of the lingering questions confronting frontline doctors caring for children like Gemma.

Efforts are under way, he said, to collaborate with other local pediatric brain cancer researchers already doing world-class work at Rady, the Sanford Burnham Prebys Medical Discovery Institute and UC San Diego.

The goal is to have genetic-sequencing capability located right below Rady’s operating room — so that genomic analysis will be immediately available to patients who need it, he said.

“Tissue from a biopsy could transfer downstairs, where it’s rapidly decoded. And this hits a big Internet pipe to Sanford Burnham, UCSD ... wherever it needs to go,” Kingsmore said. “Then they’re able to take that information and quickly figure out what’s mutated, which pieces of the genome are broken and how likely is that to be causative. You’ve got all of this data coming together in parallel so you have backup solutions being worked on while this poor kid is going through therapy. That is the vision.”

It’s a vision similar to those at other top pediatric research centers nationwide.

Dr. Mark Kieran, director of the pediatric Medical Neuro-Oncology Institute at Harvard Medical School in Boston, said his group has been sequencing all brain tumors it encounters for several years. He has experienced significant success in linking an existing cancer drug for adults to the BRAF mutation present in tumors like Gemma’s.

He said because pediatric brain tumors and neurological cancers are so much rarer in children than in adults, making progress in this specialty will likely involve finding more ways to adjust cancer medications for adults so they work in children. That can be challenged without further philanthropy: Government research dollars tend to follow the leading cancers affecting adults.

Another challenge is to determine which mutations are common across different cancers in adults and then search for similarities and contrasts in children.

“(While) these tumors look different under a microscope, we’re learning that there can be a commonality deep inside,” Kieran said.

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