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Children’s Hospital of Pittsburgh Study Points to New Approaches to Cancer Treatment

Results of Study Published by the National Academy of Sciences

A study conducted at Children’s Hospital of Pittsburgh shows that by inhibiting the action of a particular enzyme in the body, doctors might be able to not just stop the growth of cancer cells but promote their death. Results of the study were published in a recent issue of the Proceedings of the National Academy of Sciences of the United States of America.

Many enzymes, or proteins, exist in the body that activate cells to grow, repair or die, including the Lyn protein and the GADD (growth arrest and DNA damage) 34 protein. Researchers at Children’s Hospital discovered that these two proteins interact with each other. Following cell damage, such as that which occurs with chemotherapy or radiation, a series of chemical reactions takes place. Either Lyn will signal cell repair and growth or GADD 34 will signal cell death. From these discoveries, Children’s researchers have determined that if the signal from Lyn to the repair and growth mechanisms in cells can be blocked, cancer cell growth might stop and cell death might begin. Lyn, which can be found in white blood cells, also has been found to be active in a majority of leukemias.

The study was led by Anatoly V. Grishin, PhD, research assistant professor of pediatrics at Children’s Hospital of Pittsburgh and the University of Pittsburgh Medical School. Seth J. Corey, MD, scientific director of the Program in Stem Cell Biology and Therapeutics at Children’s Hospital, co-director of the Program in Hematologic Malignancies at the University of Pittsburgh Cancer Institute, and associate professor of pediatrics and pharmacology at the University of Pittsburgh School of Medicine, also participated in the study. The research was supported by grants from Cure for Lymphoma Foundation, Hirtzel Foundation, American Cancer Society and National Institutes of Health.

The results of this study have led researchers at Children’s to conclude that drug therapies could be developed in the future to block Lyn's growth and repair signals to cancer cells and, at the same time, enhance GADD 34's signals to the cells to die.

“A combination of drugs could be used to treat previously drug-resistant cancers,” Dr. Grishin said. “One drug would induce cell death and another drug would prevent cells from surviving. However, this is a fundamental discovery and we need to learn more about those mechanisms before we can recommend specific therapies.”

In fact, this study is one of many studies currently being conducted at Children’s on the Lyn protein. Researchers are studying mice that do not have the Lyn protein in their bodies-how their cells behave and how they respond to ultraviolet damage, radiation and chemotherapy. They also are studying Lyn's contribution to cell growth, the other proteins in the body that interact with Lyn and Lyn's structure. Children’s researchers plan to continue to identify mechanisms by which Lyn regulates DNA damage and how these mechanisms might be exploited to enhance chemotherapy.

“The idea behind our research is to understand the mechanisms of cancer growth,” said Dr. Corey. “We need to identify new targets for drug development and validate those targets as being important for cancer development. Once we've done that, we must convince drug companies to make a tolerable, nontoxic, preferably oral drug that people can take with minimal side effects and maximum effectiveness.”

Melanie Tush Finnigan, 412-692-5016,

Last Update
February 20, 2008
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Last Update
February 20, 2008