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Sci. Signal., 8 December 2009
Vol. 2, Issue 100, p. ra80
[DOI: 10.1126/scisignal.2000643]

RESEARCH ARTICLES

Editor's Summary

Addicted to Only a Few
Sometimes cancer cells become dependent on a particular aberrantly activated protein, encoded by an oncogene. Thus, inhibiting the activity of such an oncogenic protein is one approach to treating cancer. Bertotti et al. found that inhibition of the oncogenic protein Met, which caused "addicted" cells to stop proliferating, only inactivated a subset of the pathways downstream of Met. They identified a signaling and transcriptional response "signature," involving Ras and phosphoinositide 3-kinase pathways, that contributed to cell-cycle arrest in response to Met inhibition in the Met-addicted cancer cells. A similar biochemical and transcriptional signature was found in response to inhibition of another oncogenic receptor tyrosine kinase, the epidermal growth factor receptor, in cells addicted to this second oncogene. Thus, cells addicted to oncogenic receptor tyrosine kinases may develop common mechanisms to sustain malignancy and therefore be susceptible to similar therapeutic interventions.

Citation: A. Bertotti, M. F. Burbridge, S. Gastaldi, F. Galimi, D. Torti, E. Medico, S. Giordano, S. Corso, G. Rolland-Valognes, B. P. Lockhart, J. A. Hickman, P. M. Comoglio, L. Trusolino, Only a Subset of Met-Activated Pathways Are Required to Sustain Oncogene Addiction. Sci. Signal. 2, ra80 (2009).

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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A Molecularly Annotated Platform of Patient-Derived Xenografts ("Xenopatients") Identifies HER2 as an Effective Therapeutic Target in Cetuximab-Resistant Colorectal Cancer.
A. Bertotti, G. Migliardi, F. Galimi, F. Sassi, D. Torti, C. Isella, D. Cora, F. Di Nicolantonio, M. Buscarino, C. Petti, et al. (2011)
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MET and KRAS Gene Amplification Mediates Acquired Resistance to MET Tyrosine Kinase Inhibitors.
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Inhibition of Src Impairs the Growth of Met-Addicted Gastric Tumors.
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