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Cancer Cell. 2010 Jun 15;17(6):547-59. doi: 10.1016/j.ccr.2010.04.026.

Integrative genomic and proteomic analyses identify targets for Lkb1-deficient metastatic lung tumors.

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  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115 USA.

Abstract

In mice, Lkb1 deletion and activation of Kras(G12D) results in lung tumors with a high penetrance of lymph node and distant metastases. We analyzed these primary and metastatic de novo lung cancers with integrated genomic and proteomic profiles, and have identified gene and phosphoprotein signatures associated with Lkb1 loss and progression to invasive and metastatic lung tumors. These studies revealed that SRC is activated in Lkb1-deficient primary and metastatic lung tumors, and that the combined inhibition of SRC, PI3K, and MEK1/2 resulted in synergistic tumor regression. These studies demonstrate that integrated genomic and proteomic analyses can be used to identify signaling pathways that may be targeted for treatment.

Copyright 2010 Elsevier Inc. All rights reserved.

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PMID:
20541700
[PubMed - indexed for MEDLINE]
PMCID:
PMC2901842
Free PMC Article

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