Children’s Hospital Los Angeles and City of Hope Researchers Receive NCI Program Project Grant to Investigate Neuroblastoma Tumor Microenvironment
$2.5 million grant to study drug resistance in pediatric cancer
LOS ANGELES (Nov. 2, 2011) - A $2.5 million grant from the National Cancer Institute (NCI)’s Tumor Microenvironment Network will enable cancer researchers from City of Hope and Children’s Hospital Los Angeles to investigate drug resistance in neuroblastoma, a type of childhood cancer that usually develops in the nervous system of children five years of age or younger. Neuroblastoma is the most common type of cancer in infants, and an estimated 650 new cases are diagnosed each year in the U.S.
Researchers believe that bone marrow provides a unique microenvironment that protects cancer cells from the effects of chemotherapy, and that malignant tumor cells develop specific signaling pathways in the bone marrow that help neuroblastoma cells survive and replicate into drug-resistant offspring. The NCI grant will establish an Environment-Mediated Drug Resistance (EMDR) center at Children’s Hospital Los Angeles, which will be one of 11 NCI Tumor Microenvironment Network centers in the United States, to help researchers better understand this process and identify possible targets for new therapies.
“Our research demonstrated that the interactions between cancer cells and normal cells in the tumor microenvironment are essential for the growth and spread of neuroblastoma cancers,” said Yves De Clerck, M.D., Principal Investigator on the grant and professor of Pediatrics and Biochemistry/Molecular Biology at the Keck School of Medicine of the University of Southern California.
“We found that one such pathway of interaction called STAT3 is persistently activated in both tumor cells and in the tumor microenvironment, and we believe that targeting STAT3 signaling in bone marrow stromal cells will inhibit EMDR for neuroblastoma,” said Hua Yu, Ph.D., co-leader, Cancer Immunotherapeutics Program at City of Hope, a National Cancer Institute comprehensive cancer center.
Yu is principal investigator for one of the two projects of the new NCI Program Project Grant. The co-principal investigator of the project is Richard Jove, Ph.D., director of Beckman Research Institute of City of Hope, and holder of the Morgan and Helen Chu Director’s Chair. The researchers are collaborating with De Clerck, the program project’s principal investigator, and his colleagues Robert Seeger, M.D., and Shahab Asgharzadeh, M.D., from The Saban Research Institute at Children’s Hospital Los Angeles.
The growth of drug-resistant cancer cells in the bone marrow contributes to cancer progression, and significantly lowers the rate of patients’ long-term disease-free survival. Researchers are studying a signaling pathway called STAT3, a protein that promotes tumor growth. They hope to identify new ways to disrupt this pathway so neuroblastomas can be more effectively treated.
With new data, investigators will aim to develop specific, targeted therapies that can be tested in pediatric clinical trials. “By inhibiting environment-mediated drug resistance, we will provide a new paradigm that will result in improved survival not only for children with neuroblastoma but also for children and adults with other types of cancer,” said Robert Seeger, M.D., director of the Cancer Research program at Children’s Hospital Los Angeles.
The investigators at both institutions credit a 2009 seed grant from ThinkCure, the official charity of the Los Angeles Dodgers, in helping researchers collaborate for the initial stages of their research, which led to securing the NIH grant at a time when many funding sources are disappearing.
“This grant was made possible to a significant extent by the collaboration we began with investigators in neuroblastoma biology at City of Hope as part of our ThinkCure initiative,” said Stuart Siegel, M.D., director of the Children’s Center for Cancer & Blood Diseases, Children’s Hospital Los Angeles.
“This is an excellent example of the benefits of such collaboration between world-class research institutions, and the dedication of ThinkCure supporters who help push forward scientific research,” added Stephen J. Forman, M.D., chair, Hematology & Hematopoietic Cell Transplantation, and Francis and Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation at City of Hope.
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