Research ArticleCancer

EGFR Signaling Through an Akt-SREBP-1–Dependent, Rapamycin-Resistant Pathway Sensitizes Glioblastomas to Antilipogenic Therapy

Sci. Signal.  15 Dec 2009:
Vol. 2, Issue 101, pp. ra82
DOI: 10.1126/scisignal.2000446

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Inhibiting Lipid Metabolism to Combat Glioblastoma

Glioblastoma, the most common form of brain cancer, is frequently lethal. Glioblastoma is often associated with increased signaling through the epidermal growth factor receptor (EGFR); however, therapeutic efforts focused on inhibiting EGFR signaling have been disappointing. Guo et al. analyzed tumor tissue removed from glioblastoma patients before and during treatment with the EGFR inhibitor lapatinib and found that EGFR signaling activated sterol regulatory element–binding protein 1 (SREBP-1), a key regulator of lipid metabolism, and increased the cellular concentrations of fatty acids. Intriguingly, inhibiting fatty acid synthesis promoted apoptosis in glioblastoma cells with substantial EGFR signaling both in vitro and when transplanted into immunodeficient mice, but not in glioblastoma cells with little EGFR signaling. Thus, inhibition of fatty acid synthesis may represent a new avenue toward treating glioblastomas driven by EGFR signaling.

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