Category Archives: Research

Developing New Tools to Fight Childhood Brain Cancer

A scalpel is precise. A hammer is not.

Yet the standard treatment for medulloblastoma – the most common malignant brain tumor in children – includes the use of both tools. The exacting precision of neurosurgery to remove the tumor from a small part of the brain is followed by radiation therapy involving the whole brain in an attempt to kill any stray cancer cells. The radiation hammers healthy brain cells as well as what remains of the medulloblastoma, causing damage to a child’s still-developing brain.

Children who survive brain cancer are often in need of life-long medical, educational and psycho-social assistance, while some may be so severely affected that they are left unable to respond to a mother’s touch or a father’s voice. Many will live the rest of their lives needing assistance with activities of daily living such as feeding, bathing and dressing.

That’s why Dr. Tobey MacDonald – a pediatric hematology and oncology specialist at the Aflac Cancer Center and Blood Disorders Service of Children’s Healthcare of Atlanta – is trying to develop tools to replace the hammer. CURE Childhood Cancer is proudly funding Dr. MacDonald’s research.

“My heart is with the kids when I see them after radiation and that is what keeps me going,” says MacDonald, who is also the Director of the Pediatric Brain Tumor Program at the Aflac Cancer Center of Children’s and an Associate Professor of Pediatrics at Emory University School of Medicine.

“The primary focus of my research is trying to uncover the biology of how brain tumors metastasize,” MacDonald says. “My reason for being here is to unlock the keys that drive these cancer cells to move from one point in the brain to another.

Eight years ago, MacDonald was co-author of a landmark paper establishing a genetic difference between medulloblastoma cancer cells that spread and cancer cells that don’t. Since that time MacDonald has been investigating the key genetic differences that are critical for allowing the tumor cells to spread in the hope that drugs can be developed to target these specific genes and proteins that have been “switched on” by the tumor.

Cancer typically metastasizes – or spreads – when cells break away from the primary tumor and circulate through the bloodstream.

“Medulloblastoma walks along the coverings of the brain – the leptomeninges,” says MacDonald. And the cell-to-cell migration that makes up newly formed metastatic clump of tumor typically isn’t very far from the site where the tumor started.

“Brain tumors almost never get outside the brain – they like the environment,” says MacDonald. It has taken the better part of a decade to determine what combination of roughly 30,000 genes trigger medulloblastoma cancer cell migration.

“We’ve been trying to hone down on what are the most critical elements in a cell, so that if you knock out one or two, you stop the tumor from moving,” says MacDonald, who was recruited to georgia this fall from the Center for Cancer and Immunology Research at Children’s National Medical Center in Washington, D.C.

Research now is focusing on Rho gTPases, a family of proteins that act as a molecular switch in the complex signaling between the components of a single cell to promote and direct the movement of the tumor cell.

“We believe we have honed in on two critical targets and have identified drugs that block the signals,” says MacDonald. But the molecular switches must be turned on and off in the proper sequence, MacDonald notes, adding, “it’s like when you turn one light switch off, another flips on.”

Testing within a test subject for one drug has already begun.. Testing of other compounds will follow. MacDonald says he hopes to begin clinical testing of the drug with children in 2011 if the preliminary results in the current test subjects look promising.

“Nature is so vastly complicated, we can obviously get thrown for a loop,” he cautions.

MacDonald, however, is optimistic his research will get a boost from the synergetic collaboration working with researchers at the Aflac Cancer Center of Children’s Healthcare of Atlanta, georgia Tech, Emory University School of Medicine and the Winship Cancer Institute.

Since arriving this summer, he has already met with biomedical engineering researchers at georgia Tech who are trying to develop a way to attract and kill migrating cancer cells – much like an ant trap attracts and kills ants.

“This is why I’m excited to be here,” says MacDonald. “This situation here is enormously collaborative.”

“CURE is proud to be supporting Dr. MacDonald’s promising research,” remarks Executive Director Kristin Connor. “We are very excited about the collaborations occurring and the promise this offers children devastated by medulloblastoma and other brain tumors.”


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Improving the Odds by Understanding the Mechanism of Chemotherapy Resistance

By Clint Williams

What is true in gangster movies is true with cancer tumors. The bad guys have bodyguards, but instead of threatening death, they try to prevent it!

Research by Dr. Kelly Goldsmith, a pediatric cancer specialist at the Aflac Cancer Center and Blood Disorders Service of Children’s Healthcare of Atlanta, is targeting the molecular bodyguards protecting particularly nasty cancer cells. CURE Childhood Cancer is proudly funding Dr. Goldsmith’s research.

Neuroblastoma is a cancer that develops in the nerve tissues of the adrenal gland, abdomen, chest and neck. Apart from brain tumors, it is the most common solid tumor among children and about half of neuroblastoma cases are found in children younger than two years old.

The gravity of a diagnosis of neuroblastoma varies according to the tumor’s classification among three risk categories: low, intermediate, and high. A low-risk tumor is highly curable, but high-risk neuroblastoma kills more than half of the children with the disease.

“The majority of those children die from recurrent disease because the cancer becomes resistant to chemotherapy,” says Goldsmith, also an Assistant Professor of Pediatrics at Emory University School of Medicine. “For this tumor, we’ve got to figure out a better way to make the children chemotherapy sensitive again or to therapeutically target the tumor without harming normal tissues.”

Apoptosis, or programmed cell death, is a method by which cells are eliminated from the body without releasing harmful substances to surrounding normal tissues. Apoptosis plays a crucial role in developing and maintaining health by eliminating old cells, unnecessary cells, and unhealthy cells, like pre-cancerous ones.

Chemotherapy and radiation kill tumor cells by triggering apoptosis. Therefore, many aggressive tumors, including neuroblastoma, have found ways to survive chemotherapy by altering their apoptosis genes.

Neuroblastoma cells depend on certain members of the Bcl-2 family of proteins to protect them from apoptosis. Other members of the Bcl-2 family, called BH3-only proteins, can trigger apoptosis.  Research by Goldsmith using small chains of amino acids mimicking BH3 proteins (BH3 peptides) has potently killed neuroblastoma cells in test tubes and neuroblastoma tumors in mice.

She has also determined what Bcl-2 proteins a tumor depends on for survival by testing small tumor organelles such as mitochondria with the same BH3 peptides.

The goal is to develop profiles of tumor cells, breaking them down to the bare essentials, to best determine what drugs to use in treatment.

But establishing the effectiveness against cancer cells in test tubes and test sujects is just one step along the way to treating children. The next phase of research, Goldsmith says, requires fresh neuroblastoma tumor tissue.

But there are many competing demands for the limited supply of tumor tissue and Goldsmith will be learning and developing techniques to make the best use of the samples.

Goldsmith is building on research she did at Children’s Hospital of Philadelphia where she was recruited from in the fall of 2009.  Goldsmith is now in Atlanta to be closer to family – and – because this is where she can best help sick children by turning research results into practical treatment.

“One thing I really like about being here is the drive to translate from bench to bedside,” Goldsmith says. “I think that is such a huge focus and here they are really trying to make it a reality.”

“CURE is proud to be supporting Dr. Goldsmith’s promising research,” remarks Executive Director Kristin Connor.  “We are very concerned with making new treatments available to children as quickly as possible. We are so pleased that Dr. Goldsmith shares these urgent concerns as she works to find cures for a very devastating form of pediatric cancer.”

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CURE Childhood Cancer Announces $1 Million in New Research Grants to the Aflac Cancer Center at Children’s Healthcare of Atlanta and Emory University

Each year with the funds we raise, CURE Childhood Cancer is committed to supporting promising research which we believe will positively impact children with cancer. year after year, we work directly with doctors and scientists to identify promising ways to target cancer cells which could lead to improved treatments and ultimately cures for children with cancer. While we know that we alone cannot cure childhood cancer, by forming partnerships like ours with the Aflac Cancer Center and Emory University and working closely together, we can continue to advance toward a cure.

“The work we are supporting here is part of a very big picture,” explains CURE’s Executive director, Kristin Connor. “It’s a single piece in the overall puzzle. We are doing our part to get the pieces to fit together.”

More than 12,700 children and adolescents less than age 20 will be diagnosed with cancer in the United States this year. The cancers affecting children have in common the alteration of cells at a molecular and genetic level which causes the cells to continue their multiplication. Signals and pathways exist that allow these cells to exploit their own survival. The altered cells live on, replicating, resulting in tumor growth that can cause pain, suffering and death. Twenty one percent (21%) of children diagnosed with cancer are not cured by today’s methods of treatment. CURE Childhood Cancer is working to make a difference for these children by exploring newer methods of treatment and, hopefully one day, prevention. We are also very concerned with improving on the ways to cure children and reducing the toxicity of treatments so that the quality of life of young survivors with a lifetime in front of them is protected and left in tact.

CURE’s 2009-2010 research grants are aimed at driving research which targets cancers at a level well beneath that of poisoning the cell. The research we are supporting moves much deeper into the genetic coding and the molecular structures of these diabolical cells.

Our 2009-2010 research initiative reflects the layers of science that are applied to our understanding of cancer cells and our best means to try to outwit them. CURE is partnering with 6 scientists to aim arrows not at a single target but at several, knowing that each effort puts us further on the road to changing a poor survival rate for a child with cancer to an outstanding one.

Specifically, the projects that make up our 2009-2010 Childhood Cancer Research Initiative are:

1. Exploiting a gene [P53] that should function to protect against the formation of cancer cells but instead allows them to form. This is done by inhibiting proteins that change the functional abilities of P53, and testing that against medulloblastoma, a childhood brain tumor. (Dr. Craig Castelino, $159,213)

2. Chemically altering a peptide so that it can be used to kill neuroblastoma cells. (Dr. Kelly Goldsmith, $89,980)

3. Developing new drug targets against leukemia by outwitting a protein that causes drug resistance in leukemia cells. (Dr. Lubring Gu, $115,991)

4. Discovering new agents against childhood brain tumors by manipulating the proteins that the tumors use to resist the effects of chemotherapy. (Dr. Tobey Macdonald, $99,998)

5. Modifying immune cells to survive longer as potential anticancer agents. (Dr. Trent Spencer, $130,000)

6. Studying an agent, berberine [BBR] that could kill cancer cells that have been chemotherapy resistant. (Dr. Muxiang Zhou, $212,996)

A common thread of these projects is the study of resistance to currently available chemotherapy and the means to exploit the proteins that allow for that resistance. These efforts aim directly at the 21% of children who are not presently being cured. Use of different tumor cell lines allows the scientists to learn if the tumor type has unique resistance characteristics and to expand their findings across several tumor types.

CURE supports research at the deepest level of genetic and molecular science. Our fervent hope is that step-by-step we will outwit, modify, and target cancer in children right out of existence.

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Experimental Immunotherapy Markedly Improves Cure Rate for Children With Neuroblastoma

Researchers from the Children’s Oncology Group (“COG”) have demonstrated that a new experimental immunotherapy treatment using the chimeric monoclonal antibody ch14.18, that targets a specific carbohydrate/lipid molecule ganglioside, GD2 which is present on the surface of neuroblastoma tumor cells and cytokines IL-2 and GM-CSF resulted in a 20% improvement in cure rates compared to the standard treatment used in the past.

The findings of the COG Phase III study were published in May 2009 online on the American Society of Clinical Oncology ASCO website

Neuroblastoma is a cancer of early childhood in which the cancer cells arise from cells of the sympathetic nervous system in the neck, chest, or abdomen. Annually, there are approximately 650 new cases of neuroblastoma diagnosed in the U.S. Neuroblastoma is the most common cancer diagnosed in the first year of life and is responsible for 15% of cancer-related deaths in children. Most patients are diagnosed as toddlers, but neuroblastoma can present in infants and older teenagers as well.

“This is the first clinical trial to document that [the] combination of anti-cancer monoclonal antibodies mAbs with cytokines natural hormones that help the immune system is an effective anti-cancer therapy,” said COG lead study investigator, Alice Yu M.D., Ph.D., Professor of Pediatrics at UCSD. She goes on further to say that: “So far, all FDA approved therapeutic anti-cancer mAbs or vaccines are directed against protein or glycoprotein antigens. More importantly, this is the first study that proves that immunotherapy is effective in improving cure rates for this childhood cancer, and we are now focusing on making sure immunotherapy can be available to all children with this disease, and that we can improve on these results in the future.”

The researchers analyzed data from 226 eligible patients with high-risk neuroblastoma with a high likelihood of treatment failure and relapse. The patients were randomized to standard therapy, which consist of intensive chemotherapy followed by autologous hematipoietic stem cell transplantation and post-transplant isoretinoin, or the experimental immunotherapy moAb ch14.18 plus cytokines IL-2 plus GM-CSF and isoretinoin post transplant. Standard therapy was well tolerated, and as anticipated, the aggressive immunotherapy had significant side effects but these were manageable. The study showed that children receiving the experimental immunotherapy had a 20% better chance of remaining disease-free, and this resulted in a significantly improved cure rates. The study was stopped early due to the benefit seen in early analyses of the trial results.

John Maris, M.D., COG Neuroblastoma Disease Committee Chair, responds, “This is the first clinical trial to show a substantive increase in cure rate in well over a decade for this highly malignant childhood cancer.” Moreover, he states, “The 20% improvement in prevention of relapse for children with neuroblastoma receiving the experimental immunotherapy makes this therapy the new standard of care.”

According to COG Group Chair, Gregory Reaman, M.D., “The clinical benefit of this approach in a notoriously recalcitrant cancer of childhood is extraordinary and COG is anxious to continue its investigation of this approach to better define the toxicities and confirm its satisfactory risk: benefit ratio.” Dr. Reaman continues, “In addition, we are hopeful that this further study will result in commercialization and FDA approval and licensing of this experimental immunotherapeutic agent so that it can be made readily available as standard therapy to all children with this dreaded disease”.

For more information about new research, visit us at

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Even in tough economic times, CURE Childhood Cancer’s commitment to research stands strong. CURE recently announced $1 million in research grants to researchers at the Aflac Cancer Center and Blood Disorders Service at Children’s Healthcare of Atlanta and Emory University, bringing CURE’s total investment in research over the last 3 years to nearly $3.2 million.

According to CURE’s Executive Director, Kristin Connor, “Research represents the true ‘nuts and bolts’ of how childhood cancer cure rates improve and how treatments are developed that cure children but also leave their quality of life intact. CURE is completely focused on and committed to driving this research – even in the toughest fundraising climate we’ve ever seen.”

Fifty years ago, nearly all children diagnosed with cancer died at the hands of the disease. Today, because of research, eight out of 10 children diagnosed with cancer can be successfully treated. A major reason for the dramatic climb in survival rates is the frequent participation of children in clinical trials. Nearly two-thirds of children with cancer participate in clinical trials. Extensively researching new therapies through clinical trials has led to the development of new and better therapies as well as methods to help children deal with the side effects of cancer treatment. However, treatments are only tested in clinical trials after they have been shown to be effective in laboratory testing. That’s where CURE comes in.

By providing the Aflac Cancer Center and Emory University with funds for investigating new and promising research areas, CURE enables their researchers to gather the preliminary data needed to secure larger national grants from organizations such as the National Cancer Institute and the National Institutes of Health.

Once we’ve helped the researchers secure these grants, they can move their work forward into clinical trials and eventually, into routine medical practice. Our hope is that, in the end, every dollar we provide in research support will generate $10-$15 in national grant funding, creating an even bigger impact in the fight against childhood cancer.

For more information on the six specific research projects we are funding, please visit our website at

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What exactly does CURE Childhood Cancer fund?

CURE Childhood Cancer’s vision is to find a cure for childhood cancer in our lifetime.  We at CURE believe this is fully attainable and in efforts to get their we focus on three areas: research into childhood cancer, the most critical and urgent needs of patients and their families and eduction to support the future caregivers and researches who work tirelessly to find a cure and be their for our families.  

What exactly does CURE fund?

  • Research into the development of “targeted therapies” – that focus only cancer cells and do not harm surrounding healthy cells. Targeted therapies are critical to ensuring that patients are spared the devastating and often life-threatening “late effects” caused by current conventional therapies
  • Basic and clinical research
  • Training of future pediatric oncologists and researchers through the fellowship program at Emory University School of Medicine
  • Emergency financial assistance for families stricken by childhood cancer
  • Professional development and continuing education efforts for nurses, family support team members, and others caring for children with cancer
  • Innovative programs that address the critical and urgent needs of patients and their families, such as meals to inpatient families, outreach at the time of diagnosis, and bereavement support 

For more information on CURE Childhood Cancer and our funding visit us at

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CURE Featured in The Non-Profit Times

CURE Childhood Cancer was featured in an article Social Butterflies Can Raise Money the April 2009 issue of  The Non-Profit Times.

The article highlights the use of online and social tools that non-profit organizations are using to increase their awareness, reach and ultimately their donations. For CURE, we are currently using such online tools as Twitter, a Blog, Facebook,, and our CURE online store (just to name a few) to raise money to fund childhood cancer research to find a cure for childhood cancer in our lifetime!

Click here to read the full article, and join us online (and offline!) to help spread the word about CURE.

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