Abstract SY26-02: Targeting lipogenesis in EGFR-activated glioblastomas

Abstract

Abstract Cancer is a disease characterized by mutational activation and enhanced dependence on oncogenic signal transduction cascades. Cancer is also characterized by major shifts in cellular metabolism, including glucose utilization and uptake, energy metabolism and lipogenesis. The molecularly circuitry linking oncogenic signal transduction cascades and therapeutically targetable metabolic circuits is only beginning to be understood. This talk will focus on glioblastoma, the most common malignant primary brain tumor of adults and one of the most lethal of all cancers. Glioblastoma is characterized by nearly universal PI3K pathway hyperactivation, including EGFR amplification and mutation. Studies leading to molecular dissection of the signaling networks linking mutated EGFR with enhanced lipogenesis will be discussed, including integration of studies performed in cell lines, in vivo models and tumor tissue from patients treated with targeted inhibitors. The talk will describe the identification of a therapeutically targetable, novel EGFR/PI3K/SREBP-1 dependent prosurvival metabolic signaling pathway, as well as recent studies linking this pathway to altered fatty acid synthesis and cholesterol homeostasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY26-02. doi:10.1158/1538-7445.AM2011-SY26-02