title: Receptor tyrosine kinase coactivation networks in cancer.
abstract: Cancer cells employ multiple mechanisms to evade tightly regulated cellular processes such as proliferation, apoptosis, and senescence. Systems-wide analyses of tumors have recently identified receptor tyrosine kinase (RTK) coactivation as an important mechanism by which cancer cells achieve chemoresistance. This mini-review discusses our current understanding of the complex and dynamic process of RTK coactivation. We highlight how systems biology and computational modeling have been employed to predict integrated signaling outcomes and cancer phenotypes downstream of RTK coactivation. We conclude by providing an outlook on the feasibility of targeting RTK networks to overcome chemoresistance in cancer.
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Xu
authors.forename: Paul H
authors.initials: PH
authors.lastname: Huang
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000628:therapy; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D020794:Receptor Protein-Tyrosine Kinases
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12867-72
references.pmid: 17646646
references.citation: Science. 2007 Oct 12;318(5848):287-90
references.pmid: 17872411
references.citation: Cell. 2007 Dec 14;131(6):1190-203
references.pmid: 18083107
references.citation: Curr Opin Chem Biol. 2006 Feb;10(1):73-80
references.pmid: 16406679
references.citation: Neoplasia. 2009 May;11(5):448-58, 2 p following 458
references.pmid: 19412429
references.citation: Cancer Res. 2009 Sep 1;69(17):6871-8
references.pmid: 19671800
references.citation: Sci Signal. 2009 Jun 30;2(77):ra31
references.pmid: 19567914
references.citation: Nature. 2007 Aug 2;448(7153):604-8
references.pmid: 17637676
references.citation: Cancer Res. 2009 Oct 15;69(20):8009-16
references.pmid: 19808973
references.citation: Mol Cancer Res. 2008 Jan;6(1):139-50
references.pmid: 18234969
references.citation: Mol Syst Biol. 2009;5:256
references.pmid: 19357636
references.citation: Mol Syst Biol. 2009;5:235
references.pmid: 19156127
references.citation: Cancer Res. 2010 Feb 1;70(3):1204-14
references.pmid: 20103628
references.citation: Mol Syst Biol. 2006;2:54
references.pmid: 17016520
references.citation: Nat Methods. 2010 Feb;7(2):148-55
references.pmid: 20101245
references.citation: J Biol Chem. 1990 Oct 5;265(28):16886-90
references.pmid: 2170359
references.citation: J Clin Invest. 2008 Jul;118(7):2609-19
references.pmid: 18568074
references.citation: J Cell Sci. 2006 Nov 15;119(Pt 22):4623-33
references.pmid: 17062641
references.citation: Cancer Res. 2008 Dec 1;68(23):9712-22
references.pmid: 19047149
references.citation: Nat Cell Biol. 2009 Nov;11(11):1287-96
references.pmid: 19838175