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Pediatric Cancer Advances of 2010

Dear Friends,
During this season of hope, I’d like to take a moment to share with you the significant advances our researchers and clinicians have made against pediatric cancer in 2010. These accomplishments bring me a great sense of optimism, not only because of the patients we have cured through our hard work in the laboratory and the clinic but because of the promise our new discoveries and technologies hold in saving those patients we currently cannot cure.

It is truly an exciting time in cancer discovery. As you will read, discoveries in cancer genetics, immunology, and cancer stem cells are leading us to new, personalized therapies that target the specific cells and cellular alterations that drive the cancer. For children, this represents a huge step forward, as this new generation of treatments will not be as toxic to healthy tissue and cells and may spare young patients the lasting side effects that often result from cancer treatment. These discoveries also offer new opportunities to better understand and make real progress against those pediatric cancers that do not respond to existing treatments. New technology is allowing us to quickly key in on these unique cancer-related cell populations and alterations so that we can get the right treatments — ones that interfere with the specific cells and cellular signals driving the cancers — to the right patients.

Of course, our work would not be possible without the support of our many donors and volunteers. You are a tremendous source of hope for all of us as you continue to help us in our mission to ensure that cancer no longer threatens the life of any child. To borrow the words of one of our volunteers, “We never know which dollar is going to lead to a cure.”

I thank you for your part in advancing pediatric cancer research and treatment and extend best wishes for a happy and healthy new year.

Donald Small, M.D., Ph.D.
Director of Pediatric Oncology
Kyle Haydock Professor of Oncology

Hope, Promise, and Progress
Pediatric Cancer Research Advances of 2010

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Misty, Art for Hope artist

Breaking News —

First Pediatric Cancer Genome Mapped

Johns Hopkins Kimmel Cancer Center researchers have led the world in mapping the genetic blueprints of several common adult cancers, and now, our scientists have become the first to decipher the genetic code of a pediatric cancer. Their findings were reported in the December 16, 2010, issue of the journal Science. Using sophisticated new gene
sequencing technologies, the team mapped the genetic sequence of medulloblastoma, the most common type of pediatric brain cancer.

As suspected, this analysis clearly shows that genetic changes in pediatric cancers are remarkably different from adult tumors. The work revealed fewer genetic alterations than are typically found in adult tumors, and the researchers believe this may make it easier to use the findings to develop new therapies. The research also uncovered epigenetic alterations, biochemical variations that occur to the environment of genes and have the ability to turn genes on and off without mutating them, as a more significant culprit in pediatric cancer than commonly thought. Using drugs to block the abnormal biochemical activity can return normal gene function and stop the development of cancer cells. Information like this, gained from gene sequencing technology, could potentially help our team change the course of some relentless childhood cancers. As a result, we hope to continue this work in other pediatric cancers.

This work also demonstrates the power of philanthropic support in changing the course of cancer. The research was supported by more than a dozen funders, including Alex’s Lemonade Stand Foundation, the Children’s Brain Tumor Foundation, and the Pediatric Brain Tumor Foundation Institute.


Dr. Patrick Brown is developing desperately needed new clinical approaches for infant acute lymphocytic leukemia (ALL). Currently, with just 20 to 40 percent of patients surviving, ALL has the most dismal survival rates of any form of childhood leukemia. Dr. Brown suspects that alterations to the FLT 3 gene, which was identified and cloned by Dr. Donald Small, may be allowing the cancer to evade treatment. He is currently leading a national study of 50 patients to test a FLT 3 inhibitor. By blocking FLT 3, Brown and team are hopeful that the cancer will respond to chemotherapy. Earlier studies showed that the drug successfully turns the gene off, and ongoing studies will confirm if it is making a difference in treatment responses.

Dr. Brown is also studying a FLT 3 inhibitor in children with acute myeloid leukemia (AML) who have relapsed after chemotherapy. About 20 percent of children with AML have FLT 3 mutations, and Brown believes it is a key reason their cancers often return after treatment. Another related study will test the FLT 3 inhibitor treatment as the first line of therapy.

In the laboratory, researchers Drs. Mark Levis and Keith Pratz are working on the next generation of FLT 3 inhibitors. The new drugs are more potent and selective for FLT 3. They will be the focus of a collaborative study of pediatric leukemia patients at the Kimmel Cancer Center and 13 other national cancer centers, known for their expertise in leukemia.

Dr. Brown’s goal is make FLT 3 inhibitors and chemotherapy effective enough to get all patients into a lasting remission so that they can undergo a bone marrow transplant, but ultimately, with continued research, he hopes that FLT 3 inhibitors and chemotherapy will cure patients so that they will not require a transplant.

Pediatric Sarcomas

Treatment for pediatric sarcomas has not changed much since the 1980s. Future advances in the care of children with sarcoma will only come from a deeper understanding of the biology of these tumors, and the translation of this understanding into clinical trials. Dr. David Loeb, M.D., Ph.D., Director of the Musculoskeletal Tumor Program, is working to drive this progress.

An exciting new area of research is in cancer stem cells. These cells represent a rare and stealth population of cells that often escapes the assault of anticancer drugs and drive the growth of tumors. Like the typical stem cell that helps form and regenerate tissue and cells, cancer stem cells are capable of limitless growth, self-renewal, and the generation of
new tumors.

In Ewing’s sarcoma, one of the most common bone tumors among adolescents, patients often go into remission, but the
cancer almost always returns, resulting in a dismal long term survival rate of just 10 percent. Researchers have long noted a discord between initial good responses to chemotherapy and ultimate chance of survival.

The Johns Hopkins team suspects that while chemotherapy destroys the bulk of the tumor, it does not get at the cancer
stem cells. These resistant cells then eventually drive the growth of tumor cells, causing the cancer to return.

Ongoing work is now focused on identifying the Ewing’s sarcoma cancer stem cell. One study is examining whether using drugs that interfere with the metabolism of cancer stem cells could kill them. Another therapy that targets a specific enzyme is being studied for its potential to kill Ewing’s sarcoma and rhabdoymosarcoma cancer stem cells. With promising early laboratory data, the team is working to move quickly to clinical trials of the drug.

Finally, researchers are studying a drug, arsenic trioxide, currently used to treat leukemia that may be toxic to the cancer stem cells. Since the drug is already FDA approved, clinical trials can be rapidly initiated.

Bone Marrow Transplantation

For pediatric patients who need bone marrow transplants (BMT) to be cured, Drs. Allen Chen and Heather Symons are working to ensure this option is available. The ability to find a matching bone marrow donor prevents many patients in need from receiving a transplant. However, a novel BMT trial using half-matched donors, is allowing many more patients to receive a bone marrow transplant. It is currently available to patients with refractory and/or relapsed high risk leukemias and lymphomas. This trial is only available at Hopkins and is helping patients in the U.S. and around the world.

Results have been favorable, with safety and toxicity comparable to matched transplants. As a result, the strategy is now being used earlier in the treatment of leukemias and lymphomas, and could soon be expanded to include children with solid tumors such as sarcoma and neuroblastoma.

In the laboratory, Dr. Symons is developing a strategy to awaken the patient’s immune system and cause it to attack tumor cells. The immune system becomes tolerant of tumor cells, but by giving donor immune cells called lymphocytes, she is able to achieve a temporary attack against the cancer. To extend the response, Dr. Symons is utilizing other tools, such as radiation therapy and cryotherapy (freezing tumor cells), to cause the immune system to recognize cancers cells as foreign and dangerous.

Dr. Christopher Gamper also is studying the regulation of the immune system and has focused on a cancer-linked biochemical activity known as DNA methylation for its ability to deactivate circulating immune system T cells. Using drugs to block T cell DNA methylation could prevent cancer cells from evading T cells. In a mouse model of an aggressive cancer, Dr. Gamper showed that demethylated T cells were more effective against tumor cells. This targeted approach could help clinicians obtain improved responses against difficult pediatric cancers without the toxicities of extensive chemotherapy and radiation treatment.

Pediatric Brain Tumors

Brain tumors are the second most common group of cancers seen in children and the most common group of solid tumors. Each year, more children die of brain tumors than any other form of pediatric cancer. The Pediatric Neuro-Oncology Program at the Johns Hopkins Kimmel Cancer Center, directed by Dr. Ken Cohen, is one of the largest of its kind in the country. Each year over 80 children are diagnosed and treated at Johns Hopkins and an additional 80 to100 second opinions are provided through our multidisciplinary program.

Therapy for these patients is very complicated because some of the mainstays of treatment for tumors in other parts of the body cannot be used as aggressively because they are too harmful to children’s brains. Surgery offers limited benefits, and treatment with radiation therapy can result in severe and long term cognitive and developmental problems for children. As a result, new treatment approaches are often used.

Arsenic appears to target certain molecular pathways important to the development of certain common pediatric brain tumors. As a result, Dr. Cohen, who also is Clinical Director of Pediatric Oncology, is leading the first trial in children to combine the drug arsenic trioxide and radiation together in the treatment of children with the most aggressive forms of brain tumors. Another trial involves the first study of a new drug that targets the common cancer-gene pathway Hedgehog in certain patients with brain and other solid tumors.

Brain stem gliomas are perhaps the most challenging of all the pediatric cancers. Despite our best efforts, there are currently no children cured of this type of cancer. In a new targeted treatment approach, the cancer drugs cetuximab and irinotecan are given to children with brain stem gliomas and another treatment-resistant form of brain cancer known as high-grade astrocytoma. The drugs work by blocking a gene pathway known to be involved in the growth of these tumors.

Honors and Awards

The Damon Runyon Foundation awarded its first-ever continuation grants, and Patrick Brown, M.D. was among the recipients, earning an additional two years of funding.

The St. Baldrick’s Foundation named Christopher Gamper, M.D., Ph.D., Rachel Rau, M.D., and Eric Raabe, M.D., a St. Baldrick’s Scholar to support their research projects in cancer immunology, leukemia, and brain tumors.

Christopher Gamper, M.D., Ph.D., was named a Hyundai Hope on Wheels Scholar for his research on activating the immune system against cancer, and Ido Paz-Priel, M.D., received a Hyundai Hope Grant to support his novel therapeutic approach to promote cancer cell death in leukemia, lymphoma, and other pediatric cancers.

The Children’s Cancer Foundation provided funding to Donald Small, M.D., Ph.D., in support of pediatric oncology research, and Christopher Gamper, M.D., Ph.D. was awarded funding for his laboratory. Donald Small, M.D., Ph.D., Director of Pediatric Oncology received the Frank A. Oski Award from the American Society of Pediatric Hematology/Oncology. The award honors leading pediatric hematology and oncology clinicians and basic scientists.

New Faculty

Eric Schafer, M.D., instructor in oncology, is a new member of the pediatric oncology program. In addition to his clinical work, he will be doing laboratory research with Patrick Brown, M.D., to develop clinical trials for children with MLL gene-rearranged leukemias. Schafer, an Optimist International Foundation Scholar, competed and earned a spot in the Johns Hopkins Graduate Training Program in Clinical Investigation. He was recently awarded a Young Investigator Award from Alex’s Lemonade Stand Foundation