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August 18, 2004: Mark Kelley, PhD, member of the IU Simon Cancer Center Osteosarcoma Clinical Care and Research Program, has discovered with other scientists a protein that may help predict survival rates and lead to better treatments such as gene therapy for osteosarcoma.

Kelley and colleagues used human osteosarcoma samples to show that high levels of the human protein, apurinic endonuclease 1 (APE1), may suggest decreased survival time and reduced response rate to chemo- and radiation therapies. They then successfully demonstrated a method, known as silencing RNA (siRNA) targeting technology, for lowering protein levels in these samples. Finally, they showed that lowering these protein levels may be a way to make osteosarcoma tumor cells less resistant and more sensitive to chemo- and radiation therapies.

The protein APE1 has an important role in repairing the damaged DNA resulting from cancer, and high levels of it are found connected with other cancers. Therefore, Kelley and colleagues have been focusing their research on APE1 levels and the role it has in osteosarcoma. Their research results were published in the June 2004 issue of Molecular Cancer Therapeutics.

Better treatment is available now than 40 years ago for osteosarcoma. The use of drug therapy before surgery especially helped increase chances of survival. However, unfortunately, some patients are still at high risk that their osteosarcoma will reoccur. This may be because the tumor cells become resistant to the chemotherapy drugs. Therefore, this resistance must be overcome to advance the osteosarcoma treatment. Previous to this study, little had been known about what caused this resistance to treatment.

A long-term goal of Kelley and colleagues is to identify DNA repair proteins such as APE1 that can help determine survival and be targeted with therapies that kill more tumor cells and have fewer side effects.

Dong Wang, PhD, Director of the Daping Hospital Cancer Center and Professor of the Third Military Medical University in China, and Meihua Luo, PhD, a post-doctoral fellow in Kelley's lab, were co-investigators on the project. The study was funded by the National Institutes of Health, the Department of Defense's Congressionally-Directed Medical Research Program, and a Riley Children's Foundation postdoctoral fellowship grant held by Luo.

PubMed Abstract...