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Sci. Signal., 16 July 2013
Vol. 6, Issue 284, p. ra58
Networks of Resistance
Although effective, pharmacological targeting of receptor tyrosine kinases (RTKs) in cancer is often associated with primary or acquired resistance. Wagner et al. performed RNAi (RNA interference) perturbations of signaling proteins and monitored changes in protein phosphorylation status to study the temporal signaling downstream of six RTKs. Using network inference algorithms, network models for each of the six RTKs were constructed. Although each RTK network contained distinct patterns of signaling and regulatory events, shared features enabled classification of the six RTKs into three distinct classes. Analysis of cancer cell lines showed that the increased abundance of RTKs within a class correlated with resistance to inhibitors targeting individual receptors of that class, suggesting that some tumor cells may be primed to resist inhibitors that target individual RTKs and that targeting multiple receptors within a class may prevent resistance.
Citation: J. P. Wagner, A. Wolf-Yadlin, M. Sevecka, J. K. Grenier, D. E. Root, D. A. Lauffenburger, G. MacBeath, Receptor Tyrosine Kinases Fall into Distinct Classes Based on Their Inferred Signaling Networks. Sci. Signal.6, ra58 (2013).
Adam A. Friedman, George Tucker, Rohit Singh, Dong Yan, Arunachalam Vinayagam, Yanhui Hu, Richard Binari, Pengyu Hong, Xiaoyun Sun, Maura Porto, Svetlana Pacifico, Thilakam Murali, Russell L. Finley, Jr., John M. Asara, Bonnie Berger, and Norbert Perrimon (25 October 2011) Sci. Signal.4 (196), rs10.
[DOI: 10.1126/scisignal.2002029] |Editor's Summary »|Abstract »|Full Text »|PDF »|Supplementary Materials »
Elizabeth M. Adler and Nancy R. Gough (29 March 2011) Sci. Signal.4 (166), eg3.
[DOI: 10.1126/scisignal.2002014] |Abstract »|Full Text »|PDF »
Albrecht Moritz, Yu Li, Ailan Guo, Judit Villén, Yi Wang, Joan MacNeill, Jon Kornhauser, Kam Sprott, Jing Zhou, Anthony Possemato, Jian Min Ren, Peter Hornbeck, Lewis C. Cantley, Steven P. Gygi, John Rush, and Michael J. Comb (24 August 2010) Sci. Signal.3 (136), ra64.
[DOI: 10.1126/scisignal.2000998] |Editor's Summary »|Abstract »|Full Text »|PDF »|Supplementary Materials »
Paul H. Huang, Alexander M. Xu, and Forest M. White (8 September 2009) Sci. Signal.2 (87), re6.
[DOI: 10.1126/scisignal.287re6] |Gloss »|Abstract »|Full Text »|PDF »
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