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Combinatorial Therapeutic Strategies for Blocking Kinase Pathways in Brain Tumors

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Book cover CNS Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Recent studies have demonstrated that robustness in oncogenic signaling networks is a key contributor of resistance to kinase inhibitor monotherapy in glioblastoma patients. In this chapter, we will review several examples where combinatorial kinase inhibition has been employed as a means to overcome chemoresistance in the laboratory setting. Additionally, we will summarize approaches by which systems-level phosphoproteomic platforms, in combination with computational tools, can be employed to develop better combinatorial therapeutic strategies and translate such discoveries from the bench to the bedside.

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References

  • Alessi, D. R., Caudwell, F. B., Andjelkovic, M., Hemmings, B. A. and Cohen, P. (1996). “Molecular basis for the substrate specificity of protein kinase B; comparison with MAPKAP kinase-1 and p70 S6 kinase.” FEBS Lett 399(3): 333–8.

    Article  PubMed  CAS  Google Scholar 

  • Amit, I., Wides, R. and Yarden, Y. (2007). “Evolvable signaling networks of receptor tyrosine kinases: relevance of robustness to malignancy and to cancer therapy.” Mol Syst Biol 3: 151.

    Article  PubMed  Google Scholar 

  • Broderick, D. K., Di, C., Parrett, T. J., Samuels, Y. R., Cummins, J. M., McLendon, R. E., Fults, D. W., Velculescu, V. E., Bigner, D. D. and Yan, H. (2004). “Mutations of PIK3CA in anaplastic oligodendrogliomas, high-grade astrocytomas, and medulloblastomas.” Cancer Res 64(15): 5048–50.

    Article  PubMed  CAS  Google Scholar 

  • Cantley, L. C. (2002). “The phosphoinositide 3-kinase pathway.” Science 296(5573): 1655–7.

    Article  PubMed  CAS  Google Scholar 

  • Chen, Z., Gibson, T. B., Robinson, F., Silvestro, L., Pearson, G., Xu, B., Wright, A., Vanderbilt, C. and Cobb, M. H. (2001). “MAP kinases.” Chem Rev 101(8): 2449–76.

    Article  PubMed  CAS  Google Scholar 

  • Cloughesy, T. F., Yoshimoto, K., Nghiemphu, P., Brown, K., Dang, J., Zhu, S., Hsueh, T., Chen, Y., Wang, W., Youngkin, D., Liau, L., Martin, N., Becker, D., Bergsneider, M., Lai, A., Green, R., Oglesby, T., Koleto, M., Trent, J., Horvath, S., Mischel, P. S., Mellinghoff, I. K. and Sawyers, C. L. (2008). “Antitumor activity of rapamycin in a Phase I trial for patients with recurrent PTEN-deficient glioblastoma.” PLoS Med 5(1): e8.

    Article  PubMed  Google Scholar 

  • de la Iglesia, N., Konopka, G., Puram, S. V., Chan, J. A., Bachoo, R. M., You, M. J., Levy, D. E., Depinho, R. A. and Bonni, A. (2008). “Identification of a PTEN-regulated STAT3 brain tumor suppressor pathway.” Genes Dev 22(4): 449–62.

    Article  PubMed  Google Scholar 

  • Dittmar, T., Husemann, A., Schewe, Y., Nofer, J. R., Niggemann, B., Zanker, K. S. and Brandt, B. H. (2002). “Induction of cancer cell migration by epidermal growth factor is initiated by specific phosphorylation of tyrosine 1248 of c-erbB-2 receptor via EGFR.” Faseb J 16(13): 1823–5.

    PubMed  CAS  Google Scholar 

  • Downward, J. (2003). “Targeting RAS signalling pathways in cancer therapy.” Nat Rev Cancer 3(1): 11–22.

    Article  PubMed  CAS  Google Scholar 

  • Ekstrand, A. J., Sugawa, N., James, C. D. and Collins, V. P. (1992). “Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N- and/or C-terminal tails.” Proc Natl Acad Sci U S A 89(10): 4309–13.

    Article  PubMed  CAS  Google Scholar 

  • Engelman, J. A., Zejnullahu, K., Mitsudomi, T., Song, Y., Hyland, C., Park, J. O., Lindeman, N., Gale, C. M., Zhao, X., Christensen, J., Kosaka, T., Holmes, A. J., Rogers, A. M., Cappuzzo, F., Mok, T., Lee, C., Johnson, B. E., Cantley, L. C. and Janne, P. A. (2007). “MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling.” Science 316(5827): 1039–43.

    Article  PubMed  CAS  Google Scholar 

  • Eyler, C. E. and Rich, J. N. (2008). “Survival of the fittest: cancer stem cells in therapeutic resistance and angiogenesis.” J Clin Oncol 26(17): 2839–45.

    Article  PubMed  CAS  Google Scholar 

  • Falsey, R. R., Marron, M. T., Gunaherath, G. M., Shirahatti, N., Mahadevan, D., Gunatilaka, A. A. and Whitesell, L. (2006). “Actin microfilament aggregation induced by withaferin A is mediated by annexin II.” Nat Chem Biol 2(1): 33–8.

    Article  PubMed  CAS  Google Scholar 

  • Fan, Q. W., Cheng, C. K., Nicolaides, T. P., Hackett, C. S., Knight, Z. A., Shokat, K. M. and Weiss, W. A. (2007). “A dual phosphoinositide-3-kinase alpha/mTOR inhibitor cooperates with blockade of epidermal growth factor receptor in PTEN-mutant glioma.” Cancer Res 67(17): 7960–5.

    Article  PubMed  CAS  Google Scholar 

  • Feldkamp, M. M., Lala, P., Lau, N., Roncari, L. and Guha, A. (1999). “Expression of activated epidermal growth factor receptors, Ras-guanosine triphosphate, and mitogen-activated protein kinase in human glioblastoma multiforme specimens.” Neurosurgery 45(6): 1442–53.

    Article  PubMed  CAS  Google Scholar 

  • Frederick, L., Wang, X. Y., Eley, G. and James, C. D. (2000). “Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas.” Cancer Res 60(5): 1383–7.

    PubMed  CAS  Google Scholar 

  • Furnari, F. B., Fenton, T., Bachoo, R. M., Mukasa, A., Stommel, J. M., Stegh, A., Hahn, W. C., Ligon, K. L., Louis, D. N., Brennan, C., Chin, L., DePinho, R. A. and Cavenee, W. K. (2007). “Malignant astrocytic glioma: genetics, biology, and paths to treatment.” Genes Dev 21(21): 2683–710.

    Article  PubMed  CAS  Google Scholar 

  • Gallia, G. L., Rand, V., Siu, I. M., Eberhart, C. G., James, C. D., Marie, S. K., Oba-Shinjo, S. M., Carlotti, C. G., Caballero, O. L., Simpson, A. J., Brock, M. V., Massion, P. P., Carson, B. S., Sr. and Riggins, G. J. (2006). “PIK3CA gene mutations in pediatric and adult glioblastoma multiforme.” Mol Cancer Res 4(10): 709–14.

    Article  PubMed  CAS  Google Scholar 

  • Gupta, S., Ramjaun, A. R., Haiko, P., Wang, Y., Warne, P. H., Nicke, B., Nye, E., Stamp, G., Alitalo, K. and Downward, J. (2007). “Binding of ras to phosphoinositide 3-kinase p110alpha is required for ras-driven tumorigenesis in mice.” Cell 129(5): 957–68.

    Article  PubMed  CAS  Google Scholar 

  • Han, Y., Caday, C. G., Nanda, A., Cavenee, W. K. and Huang, H. J. (1996). “Tyrphostin AG 1478 preferentially inhibits human glioma cells expressing truncated rather than wild-type epidermal growth factor receptors.” Cancer Res 56(17): 3859–61.

    PubMed  CAS  Google Scholar 

  • Hartmann, C., Bartels, G., Gehlhaar, C., Holtkamp, N. and von Deimling, A. (2005). “PIK3CA mutations in glioblastoma multiforme.” Acta Neuropathol 109(6): 639–42.

    Article  PubMed  CAS  Google Scholar 

  • Hay, N. (2005). “The Akt-mTOR tango and its relevance to cancer.” Cancer Cell 8(3): 179–83.

    Article  PubMed  CAS  Google Scholar 

  • Hornberg, J. J., Binder, B., Bruggeman, F. J., Schoeberl, B., Heinrich, R. and Westerhoff, H. V. (2005). “Control of MAPK signalling: from complexity to what really matters.” Oncogene 24(36): 5533–42.

    Article  PubMed  CAS  Google Scholar 

  • Huang, P. H., Cavenee, W. K., Furnari, F. B. and White, F. M. (2007a). “Uncovering therapeutic targets for glioblastoma: a systems biology approach.” Cell Cycle 6(22): 2750–4.

    Article  PubMed  CAS  Google Scholar 

  • Huang, P. H., Mukasa, A., Bonavia, R., Flynn, R. A., Brewer, Z. E., Cavenee, W. K., Furnari, F. B. and White, F. M. (2007b). “Quantitative analysis of EGFRvIII cellular signaling networks reveals a combinatorial therapeutic strategy for glioblastoma.” Proc Natl Acad Sci U S A 104(31): 12867–72.

    Article  PubMed  CAS  Google Scholar 

  • Hutterer, M., Knyazev, P., Abate, A., Reschke, M., Maier, H., Stefanova, N., Knyazeva, T., Barbieri, V., Reindl, M., Muigg, A., Kostron, H., Stockhammer, G. and Ullrich, A. (2008). “Axl and growth arrest-specific gene 6 are frequently overexpressed in human gliomas and predict poor prognosis in patients with glioblastoma multiforme.” Clin Cancer Res 14(1): 130–8.

    Article  PubMed  CAS  Google Scholar 

  • Irish, J. M., Hovland, R., Krutzik, P. O., Perez, O. D., Bruserud, O., Gjertsen, B. T. and Nolan, G. P. (2004). “Single cell profiling of potentiated phospho-protein networks in cancer cells.” Cell 118(2): 217–28.

    Article  PubMed  CAS  Google Scholar 

  • Janes, K. A., Albeck, J. G., Gaudet, S., Sorger, P. K., Lauffenburger, D. A. and Yaffe, M. B. (2005). “A systems model of signaling identifies a molecular basis set for cytokine-induced apoptosis.” Science 310(5754): 1646–53.

    Article  PubMed  CAS  Google Scholar 

  • Ji, H., Zhao, X., Yuza, Y., Shimamura, T., Li, D., Protopopov, A., Jung, B. L., McNamara, K., Xia, H., Glatt, K. A., Thomas, R. K., Sasaki, H., Horner, J. W., Eck, M., Mitchell, A., Sun, Y., Al-Hashem, R., Bronson, R. T., Rabindran, S. K., Discafani, C. M., Maher, E., Shapiro, G. I., Meyerson, M. and Wong, K. K. (2006). “Epidermal growth factor receptor variant III mutations in lung tumorigenesis and sensitivity to tyrosine kinase inhibitors.” Proc Natl Acad Sci U S A 103(20): 7817–22.

    Article  PubMed  CAS  Google Scholar 

  • Johns, T. G., Luwor, R. B., Murone, C., Walker, F., Weinstock, J., Vitali, A. A., Perera, R. M., Jungbluth, A. A., Stockert, E., Old, L. J., Nice, E. C., Burgess, A. W. and Scott, A. M. (2003). “Antitumor efficacy of cytotoxic drugs and the monoclonal antibody 806 is enhanced by the EGF receptor inhibitor AG1478.” Proc Natl Acad Sci U S A 100(26): 15871–6.

    Article  PubMed  CAS  Google Scholar 

  • Koochekpour, S., Jeffers, M., Rulong, S., Taylor, G., Klineberg, E., Hudson, E. A., Resau, J. H. and Vande Woude, G. F. (1997). “Met and hepatocyte growth factor/scatter factor expression in human gliomas.” Cancer Res 57(23): 5391–8.

    PubMed  CAS  Google Scholar 

  • Learn, C. A., Hartzell, T. L., Wikstrand, C. J., Archer, G. E., Rich, J. N., Friedman, A. H., Friedman, H. S., Bigner, D. D. and Sampson, J. H. (2004). “Resistance to tyrosine kinase inhibition by mutant epidermal growth factor receptor variant III contributes to the neoplastic phenotype of glioblastoma multiforme.” Clin Cancer Res 10(9): 3216–24.

    Article  PubMed  CAS  Google Scholar 

  • Manning, B. D. and Cantley, L. C. (2007). “AKT/PKB signaling: navigating downstream.” Cell 129(7): 1261–74.

    Article  PubMed  CAS  Google Scholar 

  • Meier-Schellersheim, M., Xu, X., Angermann, B., Kunkel, E. J., Jin, T. and Germain, R. N. (2006). “Key role of local regulation in chemosensing revealed by a new molecular interaction-based modeling method.” PLoS Comput Biol 2(7): e82.

    Article  PubMed  Google Scholar 

  • Mellinghoff, I. K., Cloughesy, T. F. and Mischel, P. S. (2007). “PTEN-mediated resistance to epidermal growth factor receptor kinase inhibitors.” Clin Cancer Res 13(2 Pt 1): 378–81.

    Article  PubMed  CAS  Google Scholar 

  • Mellinghoff, I. K., Wang, M. Y., Vivanco, I., Haas-Kogan, D. A., Zhu, S., Dia, E. Q., Lu, K. V., Yoshimoto, K., Huang, J. H., Chute, D. J., Riggs, B. L., Horvath, S., Liau, L. M., Cavenee, W. K., Rao, P. N., Beroukhim, R., Peck, T. C., Lee, J. C., Sellers, W. R., Stokoe, D., Prados, M., Cloughesy, T. F., Sawyers, C. L. and Mischel, P. S. (2005). “Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors.” N Engl J Med 353(19): 2012–24.

    Article  PubMed  CAS  Google Scholar 

  • Montgomery, R. B., Moscatello, D. K., Wong, A. J., Cooper, J. A. and Stahl, W. L. (1995). “Differential modulation of mitogen-activated protein (MAP) kinase/extracellular signal-related kinase kinase and MAP kinase activities by a mutant epidermal growth factor receptor.” J Biol Chem 270(51): 30562–6.

    Article  PubMed  CAS  Google Scholar 

  • Moscatello, D. K., Holgado-Madruga, M., Emlet, D. R., Montgomery, R. B. and Wong, A. J. (1998). “Constitutive activation of phosphatidylinositol 3-kinase by a naturally occurring mutant epidermal growth factor receptor.” J Biol Chem 273(1): 200–6.

    Article  PubMed  CAS  Google Scholar 

  • Nyati, M. K., Morgan, M. A., Feng, F. Y. and Lawrence, T. S. (2006). “Integration of EGFR inhibitors with radiochemotherapy.” Nat Rev Cancer 6(11): 876–85.

    Article  PubMed  CAS  Google Scholar 

  • Ohgaki, H., Dessen, P., Jourde, B., Horstmann, S., Nishikawa, T., Di Patre, P. L., Burkhard, C., Schuler, D., Probst-Hensch, N. M., Maiorka, P. C., Baeza, N., Pisani, P., Yonekawa, Y., Yasargil, M. G., Lutolf, U. M. and Kleihues, P. (2004). “Genetic pathways to glioblastoma: a population-based study.” Cancer Res 64(19): 6892–9.

    Article  PubMed  CAS  Google Scholar 

  • Ohgaki, H. and Kleihues, P. (2007). “Genetic pathways to primary and secondary glioblastoma.” Am J Pathol 170(5): 1445–53.

    Article  PubMed  CAS  Google Scholar 

  • Okabayashi, Y., Kido, Y., Okutani, T., Sugimoto, Y., Sakaguchi, K. and Kasuga, M. (1994). “Tyrosines 1148 and 1173 of activated human epidermal growth factor receptors are binding sites of Shc in intact cells.” J Biol Chem 269(28): 18674–8.

    PubMed  CAS  Google Scholar 

  • Olsen, J. V., Blagoev, B., Gnad, F., Macek, B., Kumar, C., Mortensen, P. and Mann, M. (2006). “Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.” Cell 127(3): 635–48.

    Article  PubMed  CAS  Google Scholar 

  • Omuro, A. M., Faivre, S. and Raymond, E. (2007). “Lessons learned in the development of targeted therapy for malignant gliomas.” Mol Cancer Ther 6(7): 1909–19.

    Article  PubMed  CAS  Google Scholar 

  • Parsons, D. W., Jones, S., Zhang, X., Lin, J. C., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Siu, I. M., Gallia, G. L., Olivi, A., McLendon, R., Rasheed, B. A., Keir, S., Nikolskaya, T., Nikolsky, Y., Busam, D. A., Tekleab, H., Diaz, L. A., Jr., Hartigan, J., Smith, D. R., Strausberg, R. L., Marie, S. K., Shinjo, S. M., Yan, H., Riggins, G. J., Bigner, D. D., Karchin, R., Papadopoulos, N., Parmigiani, G., Vogelstein, B., Velculescu, V. E. and Kinzler, K. W. (2008). “An Integrated Genomic Analysis of Human Glioblastoma Multiforme.” Science 321(5897): 1807–12.

    Google Scholar 

  • Pedersen, M. W., Pedersen, N., Ottesen, L. H. and Poulsen, H. S. (2005). “Differential response to gefitinib of cells expressing normal EGFR and the mutant EGFRvIII.” Br J Cancer 93(8): 915–23.

    Article  PubMed  CAS  Google Scholar 

  • Perez, O. D. and Nolan, G. P. (2006). “Phospho-proteomic immune analysis by flow cytometry: from mechanism to translational medicine at the single-cell level.” Immunol Rev 210: 208–28.

    Article  PubMed  CAS  Google Scholar 

  • Radimerski, T., Montagne, J., Hemmings-Mieszczak, M. and Thomas, G. (2002). “Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signaling.” Genes Dev 16(20): 2627–32.

    Article  PubMed  CAS  Google Scholar 

  • Rescher, U., Ludwig, C., Konietzko, V., Kharitonenkov, A. and Gerke, V. (2008). “Tyrosine phosphorylation of annexin A2 regulates Rho-mediated actin rearrangement and cell adhesion.” J Cell Sci 121(Pt 13): 2177–85.

    Article  PubMed  CAS  Google Scholar 

  • Rich, J. N., Reardon, D. A., Peery, T., Dowell, J. M., Quinn, J. A., Penne, K. L., Wikstrand, C. J., Van Duyn, L. B., Dancey, J. E., McLendon, R. E., Kao, J. C., Stenzel, T. T., Ahmed Rasheed, B. K., Tourt-Uhlig, S. E., Herndon, J. E., 2nd, Vredenburgh, J. J., Sampson, J. H., Friedman, A. H., Bigner, D. D. and Friedman, H. S. (2004). “Phase II trial of gefitinib in recurrent glioblastoma.” J Clin Oncol 22(1): 133–42.

    Article  PubMed  CAS  Google Scholar 

  • Sampaio, C., Dance, M., Montagner, A., Edouard, T., Malet, N., Perret, B., Yart, A., Salles, J. P. and Raynal, P. (2008). “Signal strength dictates phosphoinositide 3-kinase contribution to Ras/extracellular signal-regulated kinase 1 and 2 activation via differential Gab1/Shp2 recruitment: consequences for resistance to epidermal growth factor receptor inhibition.” Mol Cell Biol 28(2): 587–600.

    Article  PubMed  CAS  Google Scholar 

  • Sarbassov, D. D., Guertin, D. A., Ali, S. M. and Sabatini, D. M. (2005). “Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex.” Science 307(5712): 1098–101.

    Article  PubMed  CAS  Google Scholar 

  • Savageau, M. A. (1971). “Parameter sensitivity as a criterion for evaluating and comparing the performance of biochemical systems.” Nature 229(5286): 542–4.

    Article  PubMed  CAS  Google Scholar 

  • Schmelzle, K. and White, F. M. (2006). “Phosphoproteomic approaches to elucidate cellular signaling networks.” Curr Opin Biotechnol 17(4): 406–14.

    Article  PubMed  CAS  Google Scholar 

  • Shankaran, H., Wiley, H. S. and Resat, H. (2007). “Receptor downregulation and desensitization enhance the information processing ability of signalling receptors.” BMC Syst Biol 1: 48.

    Article  PubMed  Google Scholar 

  • Stommel, J. M., Kimmelman, A. C., Ying, H., Nabioullin, R., Ponugoti, A. H., Wiedemeyer, R., Stegh, A. H., Bradner, J. E., Ligon, K. L., Brennan, C., Chin, L. and DePinho, R. A. (2007). “Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies.” Science 318(5848): 287–90.

    Article  PubMed  CAS  Google Scholar 

  • Sugawa, N., Ekstrand, A. J., James, C. D. and Collins, V. P. (1990). “Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas.” Proc Natl Acad Sci U S A 87(21): 8602–6.

    Article  PubMed  CAS  Google Scholar 

  • The Cancer Genome Atlas Research Network, McLendon, R., Friedman, A., Bigner, D., Van Meir, E. G., Brat, D. J., Mastrogianakis, M., Olson, J. J., Mikkelsen, T., Lehman, N., Aldape, K., Alfred Yung, W. K., Bogler, O., Vandenberg, S., Berger, M., Prados, M., Muzny, D., Morgan, M., Scherer, S., Sabo, A., Nazareth, L., Lewis, L., Hall, O., Zhu, Y., Ren, Y., Alvi, O., Yao, J., Hawes, A., Jhangiani, S., Fowler, G., San Lucas, A., Kovar, C., Cree, A., Dinh, H., Santibanez, J., Joshi, V., Gonzalez-Garay, M. L., Miller, C. A., Milosavljevic, A., Donehower, L., Wheeler, D. A., Gibbs, R. A., Cibulskis, K., Sougnez, C., Fennell, T., Mahan, S., Wilkinson, J., Ziaugra, L., Onofrio, R., Bloom, T., Nicol, R., Ardlie, K., Baldwin, J., Gabriel, S., Lander, E. S., Ding, L., Fulton, R. S., McLellan, M. D., Wallis, J., Larson, D. E., Shi, X., Abbott, R., Fulton, L., Chen, K., Koboldt, D. C., Wendl, M. C., Meyer, R., Tang, Y., Lin, L., Osborne, J. R., Dunford-Shore, B. H., Miner, T. L., Delehaunty, K., Markovic, C., Swift, G., Courtney, W., Pohl, C., Abbott, S., Hawkins, A., Leong, S., Haipek, C., Schmidt, H., Wiechert, M., Vickery, T., Scott, S., Dooling, D. J., Chinwalla, A., Weinstock, G. M., Mardis, E. R., Wilson, R. K., Getz, G., Winckler, W., Verhaak, R. G., Lawrence, M. S., O'Kelly, M., Robinson, J., Alexe, G., Beroukhim, R., Carter, S., Chiang, D., Gould, J., Gupta, S., Korn, J., Mermel, C., Mesirov, J., Monti, S., Nguyen, H., Parkin, M., Reich, M., Stransky, N., Weir, B. A., Garraway, L., Golub, T., Meyerson, M., Chin, L., Protopopov, A., Zhang, J., Perna, I., Aronson, S., Sathiamoorthy, N., Ren, G., Yao, J., Wiedemeyer, W. R., Kim, H., Won Kong, S., Xiao, Y., Kohane, I. S., Seidman, J., Park, P. J., Kucherlapati, R., Laird, P. W., Cope, L., Herman, J. G., Weisenberger, D. J., Pan, F., Van Den Berg, D., Van Neste, L., Mi Yi, J., Schuebel, K. E., Baylin, S. B., Absher, D. M., Li, J. Z., Southwick, A., Brady, S., Aggarwal, A., Chung, T., Sherlock, G., Brooks, J. D., Myers, R. M., Spellman, P. T., Purdom, E., Jakkula, L. R., Lapuk, A. V., Marr, H., Dorton, S., Gi Choi, Y., Han, J., Ray, A., Wang, V., Durinck, S., Robinson, M., Wang, N. J., Vranizan, K., Peng, V., Van Name, E., Fontenay, G. V., Ngai, J., Conboy, J. G., Parvin, B., Feiler, H. S., Speed, T. P., Gray, J. W., Brennan, C., Socci, N. D., Olshen, A., Taylor, B. S., Lash, A., Schultz, N., Reva, B., Antipin, Y., Stukalov, A., Gross, B., Cerami, E., Qing Wang, W., Qin, L. X., Seshan, V. E., Villafania, L., Cavatore, M., Borsu, L., Viale, A., Gerald, W., Sander, C., Ladanyi, M., Perou, C. M., Neil Hayes, D., Topal, M. D., Hoadley, K. A., Qi, Y., Balu, S., Shi, Y., Wu, J., Penny, R., Bittner, M., Shelton, T., Lenkiewicz, E., Morris, S., Beasley, D., Sanders, S., Kahn, A., Sfeir, R., Chen, J., Nassau, D., Feng, L., Hickey, E., Zhang, J., Weinstein, J. N., Barker, A., Gerhard, D. S., Vockley, J., Compton, C., Vaught, J., Fielding, P., Ferguson, M. L., Schaefer, C., Madhavan, S., Buetow, K. H., Collins, F., Good, P., Guyer, M., Ozenberger, B., Peterson, J. and Thomson, E. (2008). “Comprehensive genomic characterization defines human glioblastoma genes and core pathways.” Nature 455(7216): 1061–8.

    Google Scholar 

  • Wang, M. Y., Lu, K. V., Zhu, S., Dia, E. Q., Vivanco, I., Shackleford, G. M., Cavenee, W. K., Mellinghoff, I. K., Cloughesy, T. F., Sawyers, C. L. and Mischel, P. S. (2006). “Mammalian target of rapamycin inhibition promotes response to epidermal growth factor receptor kinase inhibitors in PTEN-deficient and PTEN-intact glioblastoma cells.” Cancer Res 66(16): 7864–9.

    Article  PubMed  CAS  Google Scholar 

  • Wolf-Yadlin, A., Hautaniemi, S., Lauffenburger, D. A. and White, F. M. (2007). “Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks.” Proc Natl Acad Sci U S A 104(14): 5860–5.

    Article  PubMed  CAS  Google Scholar 

  • Wolf-Yadlin, A., Kumar, N., Zhang, Y., Hautaniemi, S., Zaman, M., Kim, H. D., Grantcharova, V., Lauffenburger, D. A. and White, F. M. (2006). “Effects of HER2 overexpression on cell signaling networks governing proliferation and migration.” Mol Syst Biol 2: 54.

    Article  PubMed  Google Scholar 

  • Wong, A. J., Ruppert, J. M., Bigner, S. H., Grzeschik, C. H., Humphrey, P. A., Bigner, D. S. and Vogelstein, B. (1992). “Structural alterations of the epidermal growth factor receptor gene in human gliomas.” Proc Natl Acad Sci U S A 89(7): 2965–9.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, Y., Wolf-Yadlin, A., Ross, P. L., Pappin, D. J., Rush, J., Lauffenburger, D. A. and White, F. M. (2005). “Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules.” Mol Cell Proteomics 4(9): 1240–50.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Biological Engineering, Massachusetts Institute of Technology, Room 56-754, 02139, Cambridge, MA, USA

    Paul H. Huang & Forest M. White

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  1. Paul H. Huang
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  1. School of Medicine, Emory University, Clifton Road 1365C, Atlanta, 30322, U.S.A.

    Erwin G. Meir

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC

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Huang, P.H., White, F.M. (2009). Combinatorial Therapeutic Strategies for Blocking Kinase Pathways in Brain Tumors. In: Meir, E. (eds) CNS Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-60327-553-8_40

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