The Basic and Translational Research program of the Children’s Center for Cancer and Blood Diseases (CCCBD) integrates laboratory and clinical expertise in the search for answers for children with cancer and blood diseases. Cancer research in the CCCBD focuses on neural tumors (brain, neuroblastoma, and retinoblastoma), acute leukemia, and sarcomas. Cancer develops within a specific environment of surrounding cells and molecules, called the tumor microenvironment, which is involved in the growth and spread of cancer and development of resistance to treatment. A major research goal is to better understand the interactions of malignant cells with host cells of the tumor microenvironment, and to then translate this knowledge into clinical applications in areas of diagnosis, risk assessment, and therapy.
Our hematology researchers are conducting pioneering research into the measurement and management of iron overload, the basic pathology of sickle cell disease, and the treatment of childhood bleeding and clotting disorders.
Here are just a few examples of the groundbreaking research being conducted by expert investigators in the CCCBD:
• The research goal of Yves A. DeClerck, MD, is to better understand the mechanisms of communication between tumor cells and their microenvironment in order to identify specific targets for therapeutic intervention.
• Robert Seeger, MD, section head for Basic and Translational Research, develops strategies that prevent macrophages (a kind of white blood cell) in the microenvironment from helping neuroblastoma cells grow and resist therapy. He has found that blocking the signals between macrophages and tumor cells renders the tumor cells more sensitive to chemotherapy.
• Thomas Coates, MD, section head of hematology, is recipient of a five-year grant from the National Heart, Lung and Blood Institute of the National Institutes of Health for research into the underlying physiology of sickle cell disease and identification of biomarkers that will aid in the development of new treatment options.
• Timothy Triche, MD, PhD, co-director of Center for Personalized Medicine at CHLA conducts research in the genomic characterization of pediatric tumors. He has made the CCCBD one of the leading institutions worldwide for diagnosing and treating pediatric sarcomas and retinoblastoma, the most common eye tumor in children.
• Leo Mascarenhas, MD, section head of oncology and director of the Clinical Trials Office at the CCCBD, designs and leads clinical trials of new agents and chemotherapy combinations for children, adolescents and young adults with sarcomas.
• Nora Heisterkamp, PhD, and fellow investigators have been researching the potential of immunotherapy, using use the body’s innate cancer-fighting ability to combat pediatric acute lymphoblastic leukemia that has become resistant to chemotherapy.
• Researcher Muller Fabbri, MD, PhD, a leader in the new field of “micro-RNAs” has identified a novel molecular link between cancer, inflammation and immunity. The implications of this discovery could lead to novel anti-tumor agents able to interfere with cross-talk between cancer cells and the surrounding tumor environment.
Our cancer research program is also exploring the human genome for answers to today’s deadliest diseases, using information about an individual’s genetic makeup to unravel the biology of their tumor. Creation of a personalized cancer screening and treatment program will help determine an individual’s risk of developing cancer, match patients with treatments that are most likely to be effective, and predict which patients are at the highest risk for recurrence of the disease. In June of 2014, CHLA became the first place to offer a whole-gene sequencing panel to patients with retinoblastoma and family members who may also have inherited the gene mutation, placing them at high risk of developing this malignant cancer of the eye.