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NCI Awards $1.7 Million To CHLA Cancer Specialist

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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 (CHLA), and a research professor of Pediatrics at USC’s Keck School of Medicine, 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 because of the resistance of cancer cells to contemporary radiation and chemo-therapy 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 Comprehen-sive Cancer Center, recently discovered that radiation-resistant cancer cells can be made radiation-sensitive by specifically inactivating a molecular target made up 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.

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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