Fatih Uckun, MD, PhD, head of Translational Research in Leukemia and Lymphoma at the Children’s Center for Cancer and Blood Diseases at Children’s Hospital Los Angeles, and a research professor of Pediatrics at the Keck School of Medicine of the University of Southern California, has been awarded $1.7 million from the National Cancer Institute (NCI) to support development of a new strategy to overcome the resistance of cancer cells to radiation therapy.
In spite of promising advances in some forms of cancer, especially childhood leukemia, the overall progress in cancer therapy has remained modest due to the resistance of cancer cells to contemporary radiation and chemotherapy regimens. A team of researchers led by Dr. Uckun, an investigator at The Saban Research Institute and a member of the Developmental Therapeutics Program of the USC Norris Comprehensive Cancer Center, has recently discovered that radiation-resistant cancer cells can be made radiation-sensitive by specifically inactivating a molecular target comprised of three important signaling proteins, namely polo-like kinase 1 (PLK1), spleen tyrosine kinase (SYK) and STAT3 transcription factor.
The group’s translational research shows that rationally designed inhibitors of this molecular target markedly improve the potency of radiation therapy in animal models of radiation-resistant cancer. With an earlier $2.5 million dollar grant from NCI and the support of the National Cancer Institute Alliance for Nanotechnology in Cancer, Dr. Uckun and his team have been developing nanoparticle formulations of these inhibitors as promising drug candidates against cancer.
The goal of this new grant is to allow Dr. Uckun to further optimize the clinical potential of his innovative strategy as part of a multidisciplinary effort to overcome radiation resistance of cancer cells. In addition, Dr. Uckun and colleagues will try to identify so-called “biomarkers” that will help clinicians predict which patients would be most likely to benefit from this new strategy.
“Our long-term goal is to develop biomarker-guided, personalized radiation therapy regimens that are both more effective and have fewer side effects,” said Dr. Uckun. “We are grateful to NCI for this opportunity to work towards a practical solution for one of the most urgent unmet challenges in cancer therapy.” The main therapeutic target for this five-year research project will be the most aggressive and radiation-resistant forms of childhood leukemia and will include detailed efficacy and safety studies to evaluate clinical potential of the lead experimental anti-cancer drug candidate.
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Children’s Hospital Los Angeles
Children’s Hospital is one of only eight children’s hospitals in the nation – and the only one in the western United States – named to the national “Honor Roll” of children’s hospitals in the 2010 U.S. News & World Report rankings. Children’s Hospital is home to The Saban Research Institute, one of the largest and most productive pediatric research facilities in the United States and is one of America's premier teaching hospitals, affiliated with the Keck School of Medicine of the University of Southern California since 1932.