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12635 E. Montview Blvd., Suite 270
Aurora, CO 80045
P: (720) 859-4149
F: (720) 859-4158
The Role of RNA Helicase DDX3 in Ewing’s Sarcoma
Investigator: Breelyn Wilky, MD (AΩA, Rutgers, Robert Wood Johnson Medical School, 2005)
Mentor:David M. Loeb, MD, PhD, mentor
Institution: Johns Hopkins University School of Medicine
Results: Sarcomas are rare but highly devastating cancers of the bone and soft tissues. The goals of my research were to investigate the importance of an enzyme, RNA helicase DDX3, in sarcoma cells, in hopes of finding a new target for treatment. We found that in many types of sarcoma, very high levels of DDX3 are detected compared to normal soft tissue cells. When production of the enzyme was inhibited in sarcoma cell lines (knockdown), the “knockdown” cells showed decreased ability to form tumors in laboratory experiments and when injected into mice. These cells were also more sensitive to treatment with some types of chemotherapy. With this evidence that DDX3 was critical for sarcoma cell function, we next treated sarcoma cells with a new DDX3 inhibitor drug, called RK-33. We found that the drug could kill sarcoma cells while sparing normal cells. RK-33 was also effective against Ewing’s sarcoma cancer stem cells, which are relatively resistant to chemotherapy and have the ability to form new tumors with greater efficiency than most of the cells in the population. Finally, we implanted mice with two different human sarcomas and treated them with RK-33 injections. We found that the sarcoma with higher levels of DDX3 responded better to RK-33, suggesting that DDX3 expression could be used to determine which tumors are more likely to respond to this treatment. Based on these results, we are now preparing to design the first human clinical trials of RK-33, focusing on sarcoma patients with tumors that have high levels of DDX3.
Updated on January 31, 2014.