Research by Type:
| Childhood Cancer Research |
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BACKGROUND AND CHALLENGES Survival rates among children with cancer have significantly improved over the past 30 years, thanks to advances in cancer research and treatment. Today, eight out of ten children will survive their cancer for five years or longer. But still, cancer ranks as the second leading cause of death for all children ages 1-14. Just this year alone, it is estimated that approximately 11,210 children under age 15 will be diagnosed, and nearly 1,320 are expected to die from the disease in the United States. Research into cancer's root causes and the subsequent development of new and more effective treatments for childhood cancers have saved tens of thousands of children's lives, and our investment in this type of research must continue until reliable cures are found. For nearly four decades, the National Foundation for Cancer Research has been funding discovery-oriented research on major childhood cancers such as leukemia, lymphoma, and brain tumors. "Seed money" from NFCR has allowed scientists to set up new laboratory experiments to test their innovative cancer-fighting ideas, and sustained funding from NFCR has enabled them to further explore promising leads. With continued financial and research commitment, many of these projects may lead to more effective anti-cancer therapeutics, saving more children's lives. Listed below are just a few notable research programs that NFCR supports focused on childhood cancers.
CREATING A MORE HOPEFUL FUTURE Developing Novel Immunotherapy to Treat Leukemia and Lymphoma The human immune system is powerful when it comes to battling invaders like bacteria, but it is very often no match for cancer cells. Cancer cells are able to trick the immune system, escape immune surveillance, and grow and spread under its radar. NFCR Project Directorscientist Laurence J.N. Cooper, M.D., Ph.D., and his research team in Houston have developed a cutting-edge technique that improves the ability of the human immune system to fight cancer. With this new technique, Dr. Cooper's team is able to genetically re-program a patient's T cells-the leading cells among all immune cells when it comes to combating cancer. These re-engineered T cells, installed with a molecular sensor, can detect a specific target molecule called CD19 that sits on the cells of non-Hodgkin lymphoma and certain types of leukemia. Once locked onto their targets, the re-engineered T cells will mount a full-blown attack to eliminate those cancer cells. Dr. Cooper's first clinical study demonstrated that CAR T cells are safe and feasible in patients with CD19+ lymphoma. With continued NFCR funding, Dr. Cooper and his team at MD Anderson Cancer Center are further improving safety of CAR T cells for the patients. Dr. Cooper's innovative treatment approach is advancing rapidly through the development process and may soon provide doctors and patients with a new weapon to use in their fight against leukemia -which accounts for more than 30% of all childhood cancers -as well as lymphoma - which accounts for 8% of all childhood cancers.
Development of Novel Anti-leukemia Therapies from MicroRNA Research A mysterious group of tiny cellular molecules, called microRNAs, do not participate in protein production in the cell as other RNA molecules do. Scientists have recently discovered that microRNAs play an important regulatory role in controlling complex processes such as normal human development and cancer. NFCR scientist, Curt I. Civin, M.D., is one of the first to take a close look at the functions of microRNAs in the formation of normal blood cells and leukemia. Using cutting-edge research techniques, the Civin team at the University of Maryland, Baltimore found that certain microRNA molecules are powerful "master regulators" that switch critical genes on and off during normal blood cell and leukemia formation. To date, the team has pinpointed two microRNAs that regulate maturation of normal blood cells, and two others that even suppress the development of leukemia. Their research further demonstrated that one of these tumor suppressor microRNAs may slow the growth, increase spontaneous death, and increase drug sensitivity of human leukemia cells. With continued efforts, Dr. Civin's team is deciphering how the microRNAs work to target normal blood formation and impact leukemia growth and survival. Dr. Civin's work in these research fronts will lay solid ground for developing novel anti-leukemia treatments and enhanced transplantation and transfusion therapies, with the hope of saving the lives of many child and adult cancer patients.
Developing More Effective Drugs for Treating Glioblastoma In fact, a recently completed Phase I clinical trial was successful and confirmed that this drug targets the brain tumors in humans and is safe for clinical application. Dr. Cavenee noted that a strategy of combining this new drug with other treatment approaches is likely to provide better therapeutic efficacy in treating glioblastoma. This novel strategy merits further investigation to evaluate its clinical potential in treating children with glioblastoma and could help save the lives of more of these young patients.His team previously identified EGFRvIII, a variant version of EGFR (Epidermal Growth Factor Receptor), which is commonly present in tumor cells in glioblastoma. EGFR-targeting therapies against this growth factor are initially effective but patients develop resistance as the glioblastomas escape these "smart drugs", allowing tumors to grow again. Recently Dr. Cavenee and his team used state-of-the-art microarray technology to identify a unique gene in glioma cells called KLHDC8A or SE1. This gene may produce the molecule that enables the gliomas to escape the attack of EGFR-targeting drugs and continue to grow through an alternative molecular pathway. Dr. Cavenee reasons that this gene may be used as a new target to overcome the resistance developed by glioablastomas. NFCR and Dr. Cavenee are working together to develop innovative therapies that combine traditional EGFR-targeted drugs with newly developed approaches to block glioblastoma's escape pathway and reduce tumor survivability, giving patients a better chance against this lethal brain cancer.
Delving Deeper into the Cause of Soft Tissue Sarcomas in Children Rhabdomyosarcoma is the most common type of sarcoma found in the soft tissues of children and accounts for 3.3% of all childhood cancers. It can occur in the head and neck, genitourinary area, trunk, and extremities. New treatments are needed for patients in which surgery is not an option or for those whose cancer has metastasized. Dr. Cavenee's lab is delving deeper into the cause of this muscle tumor by focusing on the protein, PAX3-FKHR, which drives the expansion of tumor precursor cells. Traditional methods for this type of research have relied upon highly sensitive antibodies that are not available. The Cavenee teamscientists has successfully developed are a technique to "tag" or follow now using a high-throughput expression analysis to identify the downstream targets genes of PAX3-FKHR fusion gene that initiate and mediate the cancer process., providing hope that targets for the development of novel treatments will soon be identified.The scientists are also determining whether the PAX3-FKHR protein regulates the expression of microRNA genes that, in turn, regulate other growth regulators. Dr. Cavenee's vital research is providing hope that targets for the development of novel treatments for rhabdomyosarcoma will soon be identified.
Computer-aided Design of Novel Drugs for Bone Cancer in Children Osteosarcoma is a rare, cancerous (malignant) bone tumor that usually develops during the period of rapid growth that occurs in adolescence, as a teenager matures into an adult. About 400 children are diagnosed each year in the U.S. If this cancer is detected at an early stage when it is localized, children have a 60-80% chance of surviving 5 years after receiving a diagnosis. But if osteosarcoma has spread to distant sites in the body at the time of diagnosis, only 15-30% of our little patients will survive 5 years. NFCR scientist, William Jorgensen, Ph.D., is a world renowned leader in computer-aided drug design, leading his team to develop, design, and apply the necessary methodology and computer software for development of novel drugs that target FGFR or fibroblast growth factor receptor. Abnormal FGFR enzyme activity is implicated in osteosarcoma as well as in some other cancer types. The Jorgensen team starts from a detailed, three-dimensional picture of the target protein and use computational methods to automatically construct potential drug molecules that fit into sites of the target protein and cause the protein to malfunction. Preliminary results have narrowed down the top 23 structurally diverse compounds after the computer visualized over 2 million compounds into the FGFR molecule. Discovery of inhibitors of FGFR enzyme through this sophisticated computer-aided design greatly reduces the time and synthesis costs to create efficacious inhibitors and has the potential to bring novel targeted therapies rapidly into the clinics, giving osteosarcoma patients hope that their cancer can be effectively treated.
NEXT STEPS: HOW YOU CAN HELP Children are our future. The research projects that NFCR is supporting today hold great promise for saving the lives of more children tomorrow. With more money, however, our scientists could ramp up their efforts and accelerate progress. That is what the urgent plight of young cancer patients and their families demands; and that is what we at NFCR are committed to making possible. When you donate to NFCR, your dollars help our scientists accomplish many important research goals aimed at developing better cancer treatment and prevention strategies. Click here to make a donation.
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