Saturday, July 11, 2015

Child Cancer Experts Say More Research Funding Critical

Despite promising new treatments and biomarker breakthroughs, researchers and foundation executives alike say the financial resources invested in potentially life-saving studies and trials remain inadequate.

 Founder and CEO Dean Crowe poses for a photograph with a few of her foundation's Rally Kids. (Photograph courtesy Christen Patterson of the Rally Foundation)

By: James Swift

Founder and CEO Dean Crowe said the catalyst for the Rally Foundation for Childhood Cancer Research was a young boy named William.

“My husband was a baseball coach and there was a kid on his team who was diagnosed with a brain tumor,” she recalled. “He went through about 18 months of treatment — brain surgery, chemotherapy and radiation.  Unfortunately 18 months later, he relapsed.”

Crowe, a former development director for Young Life, visited William while he was hospitalized. That day, the young boy almost succumbed to the disease.

“I was so taken aback by what I saw,” Crowe said. “When I saw how sick William was, I asked his mother if we could help her … she said to raise money for childhood cancer research and find the best research we could find, no matter where it was.”

The foundation received official 501(c)(3) nonprofit status in September 2005. Over the last decade, the organization has experienced tremendous growth; raising about $5,000 in its first year, Rally handed out approximately $1.7 million in its latest round of grants issued last spring.

Originally, Crowe said the Rally strategy was to redirect funding from adult cancer research to childhood research. Early on, she said she noticed large discrepancies in the amount of money going towards adult cancer studies and trials compared to pediatric research.

“There really is a huge gap in funding for childhood cancer research,“ she said, “because it’s not profitable for the industry.”

The hard data provided by the National Institutes of Health backs up Crowe's statement. For the 2014 fiscal year, approximately $5.4 billion in federal funding went towards general cancer research.

The same year, just $276 million was allocated for pediatric cancer studies.

The Rally Approach

While some foundations focus exclusively on particular types of child cancer, Crowe said her organization seeks funding for all varieties of pediatric oncology research.

“Rally empowers volunteers all around the country to raise money specifically for childhood cancer research, so there are better treatments with fewer long-term side effects,” she said. “Basically, if you have an idea and you want to raise money for childhood cancer research, we will help you make it happen.”

The foundation employs a competitive peer-review process to select grant recipients. The organization’s medical advisory board, Crowe said, consists of some of the leading cancer researchers across North America.

Dr. Marta Sanchez-Martin, of Columbia University's Institute for Cancer
Genetics, is just one of the many pediatric oncology researchers
whose promising work has received funding from the Rally Foundation.

(Photograph courtesy Christen Patterson of the Rally Foundation)
"Several Rally-funded research projects where we were the initial investors have gone on to receive federal funding and/or gone from science at the bench to clinical trials," she said. "This speaks volumes to the quality of the research Rally funds through its competitive peer review process."

With government funding for pediatric oncology research few and far between, Crowe said their grants are necessary to keep specialists and investigators in the field.

“We fund second and third year fellows, which are doctors who finish their residencies and want to specialize in pediatric oncology,” she said. “We also give grants to what’s called junior faculty, fellows who have finished fellowships, who want to continue doing child cancer research.”

Among the Atlanta-headquartered organization’s biggest fundraisers are the Delta Double Play -- a dinner and auction coupled with a celebrity softball game hosted by Ashley and Brian McCann -- and Rally on the Runway, a fashion show featuring pediatric cancer patients escorted by pro football players.

“We kind of look at ourselves as philanthropic investors,” Crowe said. “We have given away more than $7 million, supporting more than 120 projects."

An independent audit, Crowe said, revealed the organization is a highly efficient one.

“We’re a lean machine,” she said. “For every dollar we bring in, 94 cents goes to support the mission.”

Battling a Different Kind of Demon

Crowe said pediatric cancer presents a unique set of challenges from adult cancers.

“When an adult gets cancer, typically, their bodies are finished growing,” she said. “When a child gets cancer, their bodies are changing, growing and developing … you never really know when a kid is going to hit a growth spurt, so it’s much more of a challenge than if you are treating an adult.”

Crowe said survival rates often hinge on when the young patients are first treated. “Some cancers, depending on the age you are diagnosed, you could have a much better outcome than if you are a little bit older or a little bit younger," she said.

The types of cancers children and adults tend to get are also different. Whereas adults are more prone to breast, colon, lung and prostate cancers, Crowe said children are more susceptible to brain tumors, solid tumors and a specific type of leukemia.

Whereas adult cancer patients generally have access to a wide range of treatments, Crowe said the options for children battling the disease are far more limited.

“For several cancers kids get, there is usually a first line of defense, so there’s something you’re going to try,” she said. “If that doesn’t work, there are not a lot of other options left for the family.”

She said there are even fewer protocols and drugs available for children who relapse.

“The barrier to care comes in there not being a lot of options available, and that’s a very frustrating thing for these parents,” Crowe said. “They know without a doubt that if there’s not a protocol, they’re taking a shot in the dark.”

The Frontlines

Dr. Simone Treiger Sredni is an assistant professor at Northwestern University’s Feinberg School of Medicine. She is also the director of a laboratory at the Stanley Manne Children’s Research Institute in Chicago, focusing on atypical teratoid thabdoid tumors (AT/RT.)

Dr. Simone Treiger Sredni shows off some Rally Foundation
wares. Without support from the Atlanta-based nonprofit, she
said it is doubtful her lab's key discoveries would have been

(Photograph courtesy Christen Patterson of the Rally Foundation)
“Rhabdoid tumors are known to be among the most aggressive tumors in pediatric oncology and they are considered to be rare,” Sredni said. “Unfortunately, they are not rare enough, as they are universally lethal.”

With AT/RT funding scarce, she said Rally has been a pivotal partner for her research.

Via funding from the nonprofit, Sredni said her lab identified a gene that is 50 times more expressed in children who present long survival periods after diagnosis. She also found microRNAs that may possibly function as new targets for therapeutic interventions.

“With Rally support, we are making great progress in developing a new animal model of rhabdoid tumor using zebrafish,” she said. “With this model, we will be able to test our discoveries and the discoveries of other scientists in a very low cost and fast way, as fish need small spaces to grow and have a fast development.”

Once the model is established, Sredni said hundreds of drugs and compounds can be tested on the tumor. Its toxic effects on other living animals will be studied as well.

Without the assistance from Crowe's nonprofit, she said it is unlikely any of the lab's key discoveries would have come to light.

“I was awarded my first Rally grant at the beginning of my research exclusive career, at a moment when we faced a complete lack of resources,” she said. “If it was not for Rally’s support, I would have been forced to move to another field of research or go back to being a practitioner pathologist.”

Dr. Josh Crispino, a Rally Foundation grantee working
at Northwestern University, said private sector funding is
"critical" to encourage more childhood cancer research.

(Photograph courtesy Christen Patterson of the Rally Foundation)
Dr. John Crispino is another professor at Northwestern. As does Sredni, he also has his own Stanley Manne pediatric oncology laboratory.

His work focuses on links between leukemia and Down syndrome.

“Children with Down syndrome have a 20-fold increased rick of developing the most common childhood cancer, B-cell acute lymphoblastic leukemia (B-ALL),” he said. “In our research, we have identified a specific gene, named DYRK1A, as being involved in the increased leukemia risk … our current experiments are aimed at determining whether inhibiting the activity of DYRK1A provides anti-tumor activity in this disease.”

With federal research dollars going elsewhere, he said the funding provided by Rally has been crucial.

“Funding from the National Institutes of Health has declined substantially in the past five years [and] this has forced some investigators out of basic research and made it more difficult for all scientists to maintain vigorous research programs,“ he said. “Funding from private organizations, such as the Rally Foundation for Childhood Cancer Research, is critical to fill the gap in funding and to encourage more research into new therapies for childhood cancers.”

Incentivizing ‘Big Pharma?’ 

Crowe said her organization is now pushing for changes to drug testing laws and regulations. By allowing drug manufacturers to try adult-approved treatments on children battling cancer, she said kids and teens have better shots at recovering -- all while giving “Big Pharma” an opportunity to increase its profits.

“In order to share an adult drug with a child, they have to share the same disease name,” she said. “If you develop an adult diabetes drug, pharma can test it also for kids with juvenile diabetes and get a six-month extension on the patent, which is huge money for the pharmaceutical companies.”

Since Rally was founded, Crowe said tremendous breakthroughs in genetics have taken place. Especially promising, she said, is emerging research on "smart drugs."

“It used to be the treatments went after the tumor, and now, because they can decode the genes, there’s something called biomarkers,” she said. “You can have a biomarker that targets the gene that causes the cancer to grow … that’s a whole new world, and it really opens up a bunch of possibilities for treatment.”

If an adult form of cancer and a childhood form of cancer share the same biomarker but not the same disease name, Crowe said analogous treatments can be pursued for both age groups.

"There wasn't knowledge about biomarkers which there is now, so we have to give pharma the economic inventive to now test drugs that target the same biomarkers," she said. "This will require a change in the law and Rally is part of that policy change."

She said she is optimistic those changes will incentivize major pharmaceutical companies to invest in a field that, traditionally, they have avoided.

“If you have a drug that’s working and you can let them test it on another cancer and extend their patent for another six months,“ she said, “the profit is going to come, so industry will test it."

Sredni also said biomarker breakthroughs could have a massive impact on childhood cancer research in the U.S.

“The federal government dedicates only 3.8 percent of the research budget for childhood cancer and, of course, rare tumors are not a priority when money is being allocated,” she said. “I see the biomarker technology and 'smart drugs' are the future of cancer treatment … the development of individualized therapies will definitely help the progress and hopefully cure cancer.”

The “smart drug” revolution, Crispino said, could also have major implications in his field of research.

“Current trends in this area include the development of ‘targeted therapies,' which would have activity against specific sub-types of B-ALL without widespread toxicity,“ he said. “The other trend is the use of immunotherapies -- leveraging the immune system to eradicate tumors.”

Virus Therapies

UAB researcher Dr. Gregory Friedman is studying targeted
immunotherapies, using a genetically-modified form of
the herpes simplex virus to attack malignant tumors.

(Photograph courtesy Christen Patterson of the Rally Foundation)
Dr. Gregory Friedman is an associate professor of pediatrics at the University of Alabama at Birmingham (UAB.) He said the Rally Foundation has been a long-time supporter of the UAB Comprehensive Cancer Center's neuro-oncology studies, allowing experimental therapies to leap from "the bench to the bedside" to help children in their battles against cancer.

"There are a lot of innovative ideas from pediatric cancer researchers that are unfunded and have to be abandoned because of the scarcity of federal grants for pediatric cancer research," he said. "While pediatric cancers occur less frequently than adult cancers, when you consider the amount of productive life years lost from childhood cancer deaths, there is a huge funding gap and an enormous need for more money to fund the next breakthrough in childhood cancer research."

His lab is investigating a new form of therapy, which uses a genetically altered form of the herpes simplex virus to target malignant brain tumors. Completely safe for normal cells, the virus retains its ability to kill tumor cells -- even those that are resistant to conventional therapies.

"We have demonstrated that pediatric brain tumors are highly sensitive to the virus," he said. "Based on these findings, we designed a clinical trial to test this therapy in children whose brain tumors have relapsed ... we expect to open this trial at UAB this year."

The virus therapy approach, he said, does much more than address the problems associated with toxic brain tumor effects.

“Current chemotherapy and radiation act like an atomic bomb and injures both cancer cells and normal cells, which can lead to toxicities and long-term disability,” he said. “‘Smart drugs’ like genetically altered viruses that act like guided missiles can target and kill cancer cells while sparing normal cells; this can lead to better outcomes and fewer side effects with improved quality of life for children with cancer."

The type of targeted virotherapy he is researching, Friedman said, may also be used to treat other forms of cancer.

"We believe that virus therapy holds great promise for improving outcomes for children with incurable brain tumors and lessening the damaging, lifelong side effects from current treatments for patients with curable tumors," he said. "We expect this novel approach can be expanded to target pediatric solid tumors outside the brain, which are likewise sensitive to the herpes virus."

The Future of Oncology 

Dr. Marta Sanchez-Martin is a researcher at Columbia University’s Institute for Cancer Genetics. Her lab is dedicated  to discovering new compounds to treat T cell acute lymphoblastic leukemia (T-ALL.)

“In particular, my aim is to identify new therapies that would enhance and stabilize anti-leukemic responses in the 60 percent of patients that harbor activating mutations of the NOTCH1 ocogene,” she said. “The discovery and characterization of such new agents simultaneously provides critical insights into the molecular pathways that drive T-ALL development and paves the way for novel therapeutic strategies to treat this devastating disease.”

Uncovering new and more accurate biomarkers, she said, will allow the detection of childhood leukemia much earlier. Furthermore, she said the “characterization” of patient’s tumors via genome sequencing will help specialists pinpoint “molecular drivers,” which could be blocked using targeted therapies.

“Such ‘smart drugs’ directed against particular oncogenes and pathways important for T-ALL will decrease treatment associated toxicities by acting mainly on the malignant cells while sparing normal cells of their effects,” she said.

Sanchez-Martin's lab has received grants from the Rally Foundation for three years. Thanks to their support, she said she and her colleagues have identified eight compounds possessing strong "anti-leukemia activity," both alone and in combination with NOTCH1 inhibitors.

While pioneering genetics-driven cancer therapies have proven highly effective, Sanchez-Martin said the staggering array of different types of tumors impacting both children and adults necessitates far more research -- and financial investments.

“Funding will allow us to begin to genetically and biochemical characterize each patient’s disease individually,” she said, “so that we can improve outcomes and decrease side-effects through personalized treatment strategies.”

Rallying Forward

The numbers from the National Cancer Institute are grim. The agency estimates nearly 16,000 children were diagnosed with some form of cancer last year in the United States; almost 2,000 of them are expected to eventually die from the disease.

“Childhood cancer is the number one disease killer of kids in America, and of the kids who survive, two-thirds of them have long-term side effects,” Crowe said. “If the cancer doesn’t kill you, it’s the treatment, because it attacks so many other organs in your body.”

Donations from the public, she said, go a long way in ensuring pediatric oncology studies happen, with financial contributors to the Rally cause having the option to earmark their funds for either clinical trials or researcher fellowships.

“It really depends on where your heart is, and your reasons for wanting to fund childhood cancer research,” she said. “They have the rest of their lives ahead of them, so how can they live a full, productive and healthy life?”

With so many young lives potentially saved by greater investments in childhood cancer research, Crowe said it is disheartening to realize simple economics might be the single biggest barrier to crucial studies.

“If you can extrapolate the emotion -- which is difficult to do when you attend so many children’s funerals or you see the side effects of the treatments they are going through -- I understand Big Pharma is there to make a profit,” she said. “They have to report to their shareholders, so what we have to do is come up with creative ways for it to be profitable for the industry to fund childhood cancer research.”

Rally-funded researchers, Crowe said, continue to show promising work. Recently, the organization awarded $75,000 to the Children's Hospital of Philadelphia for childhood leukemia research, additionally granting the Dana-Farber Cancer Institute $50,000 for leukemia and Ewing’s Sarcoma research. 

Other 2015 Rally grant recipients include Johns Hopkins University, granted $50,000 for relapsed leukemia, stem cell transplant and sarcoma research, and Virginia Commonwealth University's Massey Cancer Center, given $46,000 for neuroblastoma research.

The initial funding from her organization, Crowe said, is pivotal. Once the grantees can demonstrate results, she said that opens the gates for continued financial support, not only from her organization, but other agencies and funding mechanisms.  

“Rally really looks at itself as an initial investor in the next great discovery," she concluded. "And if that research shows promise, we can continue to fund it.”

Uncommon Journalism, 2015.

No comments:

Post a Comment