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A hijacking of healthy cellular circuits
Date:4/8/2013

April 8, 2013, New York, NY and San Diego Calif. Proteins that control cell growth are often mutated in cancer, and their aberrant signaling drives the wild proliferation of cells that gives rise to tumors. One such protein, the epidermal growth factor receptor (EGFR), fuels a wide variety of cancersincluding a highly malignant brain cancer known as glioblastoma. Yet drugs devised to block its signaling tend to work only for a short while, until the cancer cells adapt to evade the therapy. So far, much of the research examining such drug resistance has focused on how mutations of other proteins in cancer cells allow them to resist drugs.

But not all drug-resistant tumors harbor those additional mutations, suggesting that they have evolved alternative resistance mechanisms. In the current issue of Cancer Discovery, a team led by Paul Mischel at the Ludwig Institute for Cancer Research and Steven Bensinger at the University of California, Los Angeles, identifies a unique mechanism by which glioblastoma cells develop resistance to drugs that target EGFR signaling. The cells accomplish this feat not through mutation, but by hijacking the signaling of a perfectly normal cell surface receptor named platelet-derived growth factor receptor-β (PDGFRβ). Targeting both receptors at once, the researchers report, prevents resistance and suppresses glioblastoma tumors in laboratory models.

"Our findings highlight the remarkable adaptability of cancer cells and how they harness multiple mechanisms to maintain the growth signals critical to their survival. These results could have implications for our understanding of a wide variety of cancers," says Mischel, MD, member of the Ludwig Institute at the University of California San Diego.

Mischel, Bensinger and their colleagues began their study by exploring how blocking EGFR alters signaling in glioblastoma cells. To do so, they transplanted into mice glioblastoma tumors that are nat
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Contact: Rachel Steinhardt
rsteinhardt@licr.org
212-450-1582
Ludwig Institute for Cancer Research
Source:Eurekalert

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