MONDAY, Dec. 21 (HealthDay News) -- Fatty acid synthesis is important for the survival of glioblastomas with a continuously active epidermal growth factor receptor (EGFR), and, inhibiting fatty acid synthesis leads to reduced tumor growth and increased tumor death, according to a study in the Dec. 15 issue of Science Signaling.
Deliang Guo, from the University of California in Los Angeles, and colleagues analyzed cellular signaling in tumor tissue from glioblastoma patients before and after treatment with the EGFR inhibitor lapatinib, as well as cultured glioblastoma cells and mice bearing glioblastomas.
The researchers found that treatment with lapatinib led to activation of the master transcriptional regulator of fatty acid synthesis, sterol regulatory element-binding protein 1, and increased the amount of fatty acids in the cell. Only glioblastomas with a constitutively active form of EGFR were sensitive to pharmacologic inhibitors of fatty acid synthesis, such as atorvastatin, leading to reduced tumor growth and increased tumor death.
"These results identify a previously undescribed EGFR-mediated pro-survival metabolic pathway and suggest new therapeutic approaches to treating EGFR-activated glioblastomas," Guo and colleagues conclude.
Abstract
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