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Scientists show how brain tumors outsmart drugs
Date:1/19/2010

Researchers at the Ludwig Institute for Cancer Research (LICR) at the University of California, San Diego School of Medicine and Moores UCSD Cancer Center have shown one way in which gliomas, a deadly type of brain tumor, can evade drugs aimed at blocking a key cell signaling protein, epidermal growth factor receptor (EGFR),that is crucial for tumor growth. In a related finding, they also proved that a particular EGFR mutation is important not only to initiate the tumor, but for its continued growth or "maintenance" as well.

The findings, which appear during the week of January 18 in an online early edition of the Proceedings of the National Academy of Sciences, provide both new insights into the behavior of gliomas as well as potential new drug targets and treatment strategies.

"The results suggest that the expression of EGFR is required for tumors to keep growing, and we've shown for the first time that there are mechanisms that the tumor is using to circumvent the need for the receptor," said Frank Furnari, PhD, associate professor of medicine at the UCSD School of Medicine and associate investigator at the San Diego branch of the LICR, adding that other cancers may use similar tactics. "We need to find out more about the signaling pathways that brain tumors use to get around targeted therapeutics, such as those directed at EGFR."

In aggressive gliomas, extra copies of the EGFR gene are produced, and half of such tumors also carry an EGFR mutation, which ramps up tumor growth and portends a poor prognosis. Clinical trials of anti-EGFR agents have been disappointing; brain tumors may respond initially, but later become resistant to the drugs. To better understand why, Furnari, Webster Cavenee, PhD, professor of medicine and director of San Diego's LICR branch, and their group wanted to find out if the mutant EGFR was needed by tumors for their continued growth.

The team including postdoctoral fellows Akitake Mu
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Contact: Steve Benowitz
sbenowitz@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert

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