USC Researchers Receive $2.5 Million to Investigate Drug Resistance in Pediatric Cancer

Photo: Yves A. DeClerck, M.D., professor of pediatrics and biochemistry/molecular biology at the Keck School of Medicine of USC


A team of researchers from Keck School of Medicine of USC-affiliated Children’s Hospital Los Angeles and City Of Hope has received a five-year, $2.5 million grant from the National Cancer Institute to establish a research center that will study drug resistance in pediatric cancer, particularly in childhood neuroblastoma.

The center, headed by Yves A. DeClerck, M.D., professor of pediatrics and biochemistry/molecular biology at the Keck School, would be one of 11 tumor microenvironment centers in the United States. Researchers with those centers hope to develop new techniques to identify cells that contribute to cancer progression and targeted therapies that can be tested in clinical trials in adult and pediatric cancers.

DeClerck’s team includes Keck School faculty members Robert Seeger, M.D., professor of pediatrics, and Shahab Asgharzadeh, M.D., assistant professor of pediatrics, as well as Hua Yu, Ph.D., and Richard Jove, Ph.D., both of the Beckman Research Institute at City of Hope. DeClerck, Seeger and Asgharzadeh are members of The Saban Research Institute of Children’s Hospital Los Angeles.

Cancer is the second leading cause of death in children, and neuroblastoma is the second leading type of solid-tumor in children with cancer. Neuroblastoma tumors initially develop in the peripheral nervous system of children who are typically 5 years of age and younger. Drug resistance is a major cause of failure to cure patients from cancer, including neuroblastoma.

The studies that will be initiated by the center are based on the hypothesis that the bone marrow, which is a common site of metastasis in neuroblastoma, provides a unique microenvironment within the body that protects the cancer cells from the effects of chemotherapy. Researchers believe that normal cells in the bone marrow activate, in tumor cells, specific signaling pathways that promote the survival of the neuroblastoma cells and allow them to replicate into drug-resistant offspring. The growth of drug-resistant cancer cells in the bone marrow contributes to cancer progression, and thereby significantly lowers the rate of long-term disease-free survival for the patient. The center’s goal is to test, in pediatric clinical trials, agents that can interfere with these pathways and prevent the development of drug resistance.

“By inhibiting pathways activated by normal cells in the tumor microenvironment responsible for 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,” DeClerck said.

This National Cancer Institute Tumor Microenvironment Network grant builds on previous collaborative work funded by ThinkCure!, the T.J. Martell Foundation and the Richard Call Family Endowed Chair in Pediatric Research Innovation that is currently held by DeClerck.

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