Uncovering therapeutic targets for glioblastoma: a systems biology approach.

TitleUncovering therapeutic targets for glioblastoma: a systems biology approach.
Publication TypeJournal Article
Year of Publication2007
AuthorsHuang, PH, Cavenee, WK, Furnari, FB, White, FM
JournalCell Cycle
Date Published2007 Nov 15
KeywordsAnimals, Brain Neoplasms, Drug Delivery Systems, Gene Expression Regulation, Neoplastic, Glioblastoma, Humans, Signal Transduction, Systems Biology

Even though glioblastoma, WHO grade IV (GBM) is one of the most devastating adult cancers, current treatment regimens have not led to any improvements in patient life expectancy or quality of life. The constitutively active EGFRvIII receptor is one of the most commonly mutated proteins in GBM and has been linked to radiation and chemotherapeutic resistance. To define the mechanisms by which this protein alters cell physiology, we have recently performed a phosphoproteomic analysis of EGFRvIII signaling networks in GBM cells. The results of this study provided important insights into the biology of this mutated receptor, including oncogene dose effects and differential utilization of signaling pathways. Moreover, clustering of the phosphoproteomic data set revealed a previously undescribed crosstalk between EGFRvIII and the c-Met receptor. Treatment of the cells with a combination employing both EGFR and c-Met kinase inhibitors dramatically decreased cell viability in vitro. In this perspective, we highlight the use of systems biology as a tool to better understand the molecular basis of GBM tumor biology as well as to uncover non-intuitive candidates for therapeutic target validation.

Alternate JournalCell Cycle
PubMed ID17986864
Grant ListP01-CA95616 / CA / NCI NIH HHS / United States
P50-GM68762 / GM / NIGMS NIH HHS / United States
U54-CA112967 / CA / NCI NIH HHS / United States

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