Research ArticleSystems Biology

Therapeutically Targeting ErbB3: A Key Node in Ligand-Induced Activation of the ErbB Receptor–PI3K Axis

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Science Signaling  30 Jun 2009:
Vol. 2, Issue 77, pp. ra31
DOI: 10.1126/scisignal.2000352

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Zooming In on ErbB3

Aberrant signaling involving the ErbB family of receptors, which can signal as homo- or heterodimers to activate the phosphatidylinositol 3-kinase (PI3K) signaling pathway, has been implicated as contributing to various cancers. Using a systems approach, Schoeberl et al. implicated ErbB3—a member of the ErbB family that is catalytically inactive—as critical to signaling stimulated by ligands that bind either ErbB1 or ErbB3. Computational analysis suggested that inhibiting ligand binding to ErbB3 might represent a more successful approach to treating cancers associated with ligand-induced stimulation of ErbB-PI3K signaling mediated by combinatorial receptor activation than do current therapies that target overexpressed or mutationally activated ErbB-family receptors. Moreover, experimental analysis revealed that a monoclonal antibody developed on the basis of this strategy could stop the growth of tumors grafted into immunodeficient mice.

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