Skip to main content
SpringerLink
Log in

Epidermal growth factor receptor and mammalian target of rapamycin as therapeutic targets in malignant glioma: current clinical status and perspectives

  • Review
  • Published:
Targeted Oncology Aims and scope Submit manuscript

Abstract

Despite advances in the understanding of the molecular biology of glioblastomas (GB), these neoplasms still are incurable with conventional therapies. Current efforts therefore focus on the development of new molecular approaches that exploit the genetic aberrations of cancer cells. Based on their frequent activation or mutation in human GB and their paramount role for the maintenance of the neoplastic phenotype, both the epidermal growth factor receptor (EGFR) and the mammalian target of rapamycin (mTOR) are plausible targets for molecular therapies. However, clinical trials with drugs targeting EGFR or mTOR, so far, have produced largely disappointing results. In this article, we review strategies targeting EGFR and mTOR as therapies for malignant glioma. Recent advances in the understanding of the complex signaling network involved are highlighted and the results of clinical trials are summarized. Mechanisms of resistance are explored, and potential future directions as well as trends in preclinical and clinical development are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    Article  CAS  PubMed  Google Scholar 

  2. Mitsudomi T, Yatabe Y (2010) Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer. FEBS J 277:301–308

    Article  CAS  PubMed  Google Scholar 

  3. Gottlieb E (2009) Cancer: the fat and the furious. Nature 461:44–45

    Article  CAS  PubMed  Google Scholar 

  4. Barnes K, Ingram JC, Porras OH, Barros LF, Hudson ER, Fryer LG, Foufelle F, Carling D, Hardie DG, Baldwin SA (2002) Activation of GLUT1 by metabolic and osmotic stress: potential involvement of AMP-activated protein kinase (AMPK). J Cell Sci 115:2433–2442

    CAS  PubMed  Google Scholar 

  5. Nose A, Mori Y, Uchiyama-Tanaka Y, Kishimoto N, Maruyama K, Matsubara H, Iwasaka T (2003) Regulation of glucose transporter (GLUT1) gene expression by angiotensin II in mesangial cells: involvement of HB-EGF and EGF receptor transactivation. Hypertens Res 26:67–73

    Article  CAS  PubMed  Google Scholar 

  6. Miyamoto S, Murphy AN, Brown JH (2008) Akt mediates mitochondrial protection in cardiomyocytes through phosphorylation of mitochondrial hexokinase-II. Cell Death Differ 15:521–529

    Article  CAS  PubMed  Google Scholar 

  7. Laplante M, Sabatini DM (2009) mTOR signaling at a glance. J Cell Sci 122:3589–3594

    Article  CAS  PubMed  Google Scholar 

  8. Ma XM, Blenis J (2009) Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol 10:307–318

    Article  PubMed  Google Scholar 

  9. O’Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D, Lane H, Hofmann F, Hicklin DJ, Ludwig DL et al (2006) mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 66:1500–1508

    Article  PubMed  Google Scholar 

  10. Sun SY, Rosenberg LM, Wang X, Zhou Z, Yue P, Fu H, Khuri FR (2005) Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition. Cancer Res 65:7052–7058

    Article  CAS  PubMed  Google Scholar 

  11. Cloughesy TF, Yoshimoto K, Nghiemphu P, Brown K, Dang J, Zhu S, Hsueh T, Chen Y, Wang W, Youngkin D et al (2008) Antitumor activity of rapamycin in a Phase I trial for patients with recurrent PTEN-deficient glioblastoma. PLoS Med 5:e8

    Article  PubMed  Google Scholar 

  12. Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM (2004) Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol 14:1296–1302

    Article  CAS  PubMed  Google Scholar 

  13. Network TCGAR (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455:1061–1068

    Article  Google Scholar 

  14. Wikstrand CJ, McLendon RE, Friedman AH, Bigner DD (1997) Cell surface localization and density of the tumor-associated variant of the epidermal growth factor receptor, EGFRvIII. Cancer Res 57:4130–4140

    CAS  PubMed  Google Scholar 

  15. Voldborg BR, Damstrup L, Spang-Thomsen M, Poulsen HS (1997) Epidermal growth factor receptor (EGFR) and EGFR mutations, function and possible role in clinical trials. Ann Oncol 8:1197–1206

    Article  CAS  PubMed  Google Scholar 

  16. Lee JC, Vivanco I, Beroukhim R, Huang JH, Feng WL, DeBiasi RM, Yoshimoto K, King JC, Nghiemphu P, Yuza Y et al (2006) Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain. PLoS Med 3:e485

    Article  PubMed  Google Scholar 

  17. Ekstrand AJ, Sugawa N, James CD, Collins VP (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 USA 89:4309–4313

    Article  CAS  PubMed  Google Scholar 

  18. Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ et al (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773

    Article  CAS  PubMed  Google Scholar 

  19. Choe G, Horvath S, Cloughesy TF, Crosby K, Seligson D, Palotie A, Inge L, Smith BL, Sawyers CL, Mischel PS (2003) Analysis of the phosphatidylinositol 3′-kinase signaling pathway in glioblastoma patients in vivo. Cancer Res 63:2742–2746

    CAS  PubMed  Google Scholar 

  20. Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD, Misra A, Nigro JM, Colman H, Soroceanu L et al (2006) Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9:157–173

    Article  CAS  PubMed  Google Scholar 

  21. Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP et al (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98–110

    Article  CAS  PubMed  Google Scholar 

  22. Lammering G, Valerie K, Lin PS, Mikkelsen RB, Contessa JN, Feden JP, Farnsworth J, Dent P, Schmidt-Ullrich RK (2001) Radiosensitization of malignant glioma cells through overexpression of dominant-negative epidermal growth factor receptor. Clin Cancer Res 7:682–690

    CAS  PubMed  Google Scholar 

  23. Nagane M, Levitzki A, Gazit A, Cavenee WK, Huang HJ (1998) Drug resistance of human glioblastoma cells conferred by a tumor-specific mutant epidermal growth factor receptor through modulation of Bcl-XL and caspase-3-like proteases. Proc Natl Acad Sci USA 95:5724–5729

    Article  CAS  PubMed  Google Scholar 

  24. Steinbach JP, Supra P, Huang HJ, Cavenee WK, Weller M (2002) CD95-mediated apoptosis of human glioma cells: modulation by epidermal growth factor receptor activity. Brain Pathol 12:12–20

    Article  CAS  PubMed  Google Scholar 

  25. Eshleman JS, Carlson BL, Mladek AC, Kastner BD, Shide KL, Sarkaria JN (2002) Inhibition of the mammalian target of rapamycin sensitizes U87 xenografts to fractionated radiation therapy. Cancer Res 62:7291–7297

    CAS  PubMed  Google Scholar 

  26. Steinbach JP, Wolburg H, Klumpp A, Weller M (2005) Hypoxia sensitizes human malignant glioma cells towards CD95L-induced cell death. J Neurochem 92:1340–1349

    Article  CAS  PubMed  Google Scholar 

  27. Steinbach JP, Klumpp A, Wolburg H, Weller M (2004) Inhibition of epidermal growth factor receptor signaling protects human malignant glioma cells from hypoxia-induced cell death. Cancer Res 64:1575–1578

    Article  CAS  PubMed  Google Scholar 

  28. Ronellenfitsch MW, Brucker DP, Burger MC, Wolking S, Tritschler F, Rieger J, Wick W, Weller M, Steinbach JP (2009) Antagonism of the mammalian target of rapamycin selectively mediates metabolic effects of epidermal growth factor receptor inhibition and protects human malignant glioma cells from hypoxia-induced cell death. Brain 132:1509–1522

    Article  PubMed  Google Scholar 

  29. Rieger J, Bähr O, Müller K, Franz K, Steinbach J, Hattingen E (2010) Bevacizumab-induced diffusion-restricted lesions in malignant glioma patients. J Neurooncol 99(1):49–56

    Article  CAS  PubMed  Google Scholar 

  30. Rieger J, Bähr O, Ronellenfitsch MW, Steinbach J, Hattingen E (2010) Bevacizumab-induced diffusion restriction in patients with glioma: tumor progression or surrogate marker of hypoxia? J Clin Oncol. doi:10.1200/JCO.2010.29.2029

    PubMed  Google Scholar 

  31. Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I et al (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271–2281

    Article  CAS  PubMed  Google Scholar 

  32. Hess G, Herbrecht R, Romaguera J, Verhoef G, Crump M, Gisselbrecht C, Laurell A, Offner F, Strahs A, Berkenblit A et al (2009) Phase III study to evaluate temsirolimus compared with investigator’s choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol 27:3822–3829

    Article  CAS  PubMed  Google Scholar 

  33. Atkins MB, Yasothan U, Kirkpatrick P (2009) Everolimus. Nat Rev Drug Discov 8:535–536

    Article  CAS  PubMed  Google Scholar 

  34. Rini B, Kar S, Kirkpatrick P (2007) Temsirolimus. Nat Rev Drug Discov 6:599–600

    Article  CAS  Google Scholar 

  35. Molckovsky A, Siu LL (2008) First-in-class, first-in-human phase I results of targeted agents: highlights of the 2008 American society of clinical oncology meeting. J Hematol Oncol 1:20

    Article  PubMed  Google Scholar 

  36. Guertin DA, Sabatini DM (2009) The pharmacology of mTOR inhibition. Sci Signal pe2:24

    Google Scholar 

  37. Brachmann S, Fritsch C, Maira SM, Garcia-Echeverria C (2009) PI3K and mTOR inhibitors: a new generation of targeted anticancer agents. Curr Opin Cell Biol 21:194–198

    Article  CAS  PubMed  Google Scholar 

  38. Neyns B, Sadones J, Joosens E, Bouttens F, Verbeke L, Baurain JF, D’Hondt L, Strauven T, Chaskis C, In’t Veld P et al (2009) Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma. Ann Oncol 20:1596–1603

    Article  CAS  PubMed  Google Scholar 

  39. Rich JN, Reardon DA, Peery T, Dowell JM, Quinn JA, Penne KL, Wikstrand CJ, Van Duyn LB, Dancey JE, McLendon RE et al (2004) Phase II trial of gefitinib in recurrent glioblastoma. J Clin Oncol 22:133–142

    Article  CAS  PubMed  Google Scholar 

  40. van den Bent MJ, Brandes AA, Rampling R, Kouwenhoven MC, Kros JM, Carpentier AF, Clement PM, Frenay M, Campone M, Baurain JF et al (2009) Randomized phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034. J Clin Oncol 27:1268–1274

    Article  PubMed  Google Scholar 

  41. Galanis E, Buckner JC, Maurer MJ, Kreisberg JI, Ballman K, Boni J, Peralba JM, Jenkins RB, Dakhil SR, Morton RF et al (2005) Phase II trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: a North Central Cancer Treatment Group Study. J Clin Oncol 23:5294–5304

    Article  CAS  PubMed  Google Scholar 

  42. Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280

    CAS  PubMed  Google Scholar 

  43. Chang SM, Wen P, Cloughesy T, Greenberg H, Schiff D, Conrad C, Fink K, Robins HI, De Angelis L, Raizer J et al (2005) Phase II study of CCI-779 in patients with recurrent glioblastoma multiforme. Invest New Drugs 23:357–361

    Article  CAS  PubMed  Google Scholar 

  44. Neshat MS, Mellinghoff IK, Tran C, Stiles B, Thomas G, Petersen R, Frost P, Gibbons JJ, Wu H, Sawyers CL (2001) Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR. Proc Natl Acad Sci USA 98:10314–10319

    Article  CAS  PubMed  Google Scholar 

  45. Podsypanina K, Lee RT, Politis C, Hennessy I, Crane A, Puc J, Neshat M, Wang H, Yang L, Gibbons J et al (2001) An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/− mice. Proc Natl Acad Sci USA 98:10320–10325

    Article  CAS  PubMed  Google Scholar 

  46. Goudar RK, Shi Q, Hjelmeland MD, Keir ST, McLendon RE, Wikstrand CJ, Reese ED, Conrad CA, Traxler P, Lane HA et al (2005) Combination therapy of inhibitors of epidermal growth factor receptor/vascular endothelial growth factor receptor 2 (AEE788) and the mammalian target of rapamycin (RAD001) offers improved glioblastoma tumor growth inhibition. Mol Cancer Ther 4:101–112

    CAS  PubMed  Google Scholar 

  47. Doherty L, Gigas DC, Kesari S, Drappatz J, Kim R, Zimmerman J, Ostrowsky L, Wen PY (2006) Pilot study of the combination of EGFR and mTOR inhibitors in recurrent malignant gliomas. Neurology 67:156–158

    Article  CAS  PubMed  Google Scholar 

  48. Kreisl TN, Lassman AB, Mischel PS, Rosen N, Scher HI, Teruya-Feldstein J, Shaffer D, Lis E, Abrey LE (2009) A pilot study of everolimus and gefitinib in the treatment of recurrent glioblastoma (GBM). J Neurooncol 92:99–105

    Article  CAS  PubMed  Google Scholar 

  49. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216

    Article  CAS  PubMed  Google Scholar 

  50. Chang SM, Kuhn J, Lamborn K, Cloughesy T, Robins I, Lieberman F, Yung A, Dancey J, Prados M, Wen P (2009) Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas (MG) (NABTC 04–02). J Clin Oncol 27:15s, (suppl; abstr 2004)

    Google Scholar 

  51. Prados MD, Chang SM, Butowski N, DeBoer R, Parvataneni R, Carliner H, Kabuubi P, Ayers-Ringler J, Rabbitt J, Page M et al (2009) Phase II study of erlotinib plus temozolomide during and after radiation therapy in patients with newly diagnosed glioblastoma multiforme or gliosarcoma. J Clin Oncol 27:579–584

    Article  CAS  PubMed  Google Scholar 

  52. Wen PY, Cloughesy T, Kuhn J, Lamborn K, Abrey LE, Lieberman F, Robins HI, Wright J, Prados MD, Gilbert M (2009) Phase I/II study of sorafenib and temsirolimus for patients with recurrent glioblastoma (GBM) (NABTC 05–02). J Clin Oncol 27:15s, (suppl; abstr 2006)

    Google Scholar 

  53. Brady LW, Miyamoto C, Woo DV, Rackover M, Emrich J, Bender H, Dadparvar S, Steplewski Z, Koprowski H, Black P et al (1992) Malignant astrocytomas treated with iodine-125 labeled monoclonal antibody 425 against epidermal growth factor receptor: a phase II trial. Int J Radiat Oncol Biol Phys 22:225–230

    CAS  PubMed  Google Scholar 

  54. Emrich JG, Brady LW, Quang TS, Class R, Miyamoto C, Black P, Rodeck U (2002) Radioiodinated (I-125) monoclonal antibody 425 in the treatment of high grade glioma patients: ten-year synopsis of a novel treatment. Am J Clin Oncol 25:541–546

    Article  PubMed  Google Scholar 

  55. Brown PD, Krishnan S, Sarkaria JN, Wu W, Jaeckle KA, Uhm JH, Geoffroy FJ, Arusell R, Kitange G, Jenkins RB et al (2008) Phase I/II trial of erlotinib and temozolomide with radiation therapy in the treatment of newly diagnosed glioblastoma multiforme: North Central Cancer Treatment Group Study N0177. J Clin Oncol 26:5603–5609

    Article  CAS  PubMed  Google Scholar 

  56. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996

    Article  CAS  PubMed  Google Scholar 

  57. Mellinghoff IK, Wang MY, Vivanco I, Haas-Kogan DA, Zhu S, Dia EQ, Lu KV, Yoshimoto K, Huang JH, Chute DJ et al (2005) Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med 353:2012–2024

    Article  CAS  PubMed  Google Scholar 

  58. Haas-Kogan DA, Prados MD, Tihan T, Eberhard DA, Jelluma N, Arvold ND, Baumber R, Lamborn KR, Kapadia A, Malec M et al (2005) Epidermal growth factor receptor, protein kinase B/Akt, and glioma response to erlotinib. J Natl Cancer Inst 97:880–887

    Article  CAS  PubMed  Google Scholar 

  59. Lassman AB, Rossi MR, Raizer JJ, Abrey LE, Lieberman FS, Grefe CN, Lamborn K, Pao W, Shih AH, Kuhn JG et al (2005) Molecular study of malignant gliomas treated with epidermal growth factor receptor inhibitors: tissue analysis from North American Brain Tumor Consortium Trials 01–03 and 00–01. Clin Cancer Res 11:7841–7850

    Article  CAS  PubMed  Google Scholar 

  60. Thoreen CC, Kang SA, Chang JW, Liu Q, Zhang J, Gao Y, Reichling LJ, Sim T, Sabatini DM, Gray NS (2009) An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem 284:8023–8032

    Article  CAS  PubMed  Google Scholar 

  61. Steinbach JP, Eisenmann C, Klumpp A, Weller M (2004) Co-inhibition of epidermal growth factor receptor and type 1 insulin-like growth factor receptor synergistically sensitizes human malignant glioma cells to CD95L-induced apoptosis. Biochem Biophys Res Commun 321:524–530

    Article  CAS  PubMed  Google Scholar 

  62. Stommel JM, Kimmelman AC, Ying H, Nabioullin R, Ponugoti AH, Wiedemeyer R, Stegh AH, Bradner JE, Ligon KL, Brennan C et al (2007) Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. Science 318:287–290

    Article  CAS  PubMed  Google Scholar 

  63. Humphrey PA, Wong AJ, Vogelstein B, Zalutsky MR, Fuller GN, Archer GE, Friedman HS, Kwatra MM, Bigner SH, Bigner DD (1990) Anti-synthetic peptide antibody reacting at the fusion junction of deletion-mutant epidermal growth factor receptors in human glioblastoma. Proc Natl Acad Sci USA 87:4207–4211

    Article  CAS  PubMed  Google Scholar 

  64. Sampson JH, Archer GE, Mitchell DA, Heimberger AB, Herndon JE 2nd, Lally-Goss D, McGehee-Norman S, Paolino A, Reardon DA, Friedman AH et al (2009) An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme. Mol Cancer Ther 8:2773–2779

    Article  CAS  PubMed  Google Scholar 

  65. Mulloy R, Ferrand A, Kim Y, Sordella R, Bell DW, Haber DA, Anderson KS, Settleman J (2007) Epidermal growth factor receptor mutants from human lung cancers exhibit enhanced catalytic activity and increased sensitivity to gefitinib. Cancer Res 67:2325–2330

    Article  CAS  PubMed  Google Scholar 

  66. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG et al (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350:2129–2139

    Article  CAS  PubMed  Google Scholar 

  67. Rich JN, Rasheed BK, Yan H (2004) EGFR mutations and sensitivity to gefitinib. N Engl J Med 351:1260–1261, author reply 1260–1261

    Article  CAS  PubMed  Google Scholar 

  68. Kummar S, Kinders R, Rubinstein L, Parchment RE, Murgo AJ, Collins J, Pickeral O, Low J, Steinberg SM, Gutierrez M et al (2007) Compressing drug development timelines in oncology using phase ‘0’ trials. Nat Rev Cancer 7:131–139

    Article  CAS  PubMed  Google Scholar 

  69. Wei LH, Su H, Hildebrandt IJ, Phelps ME, Czernin J, Weber WA (2008) Changes in tumor metabolism as readout for Mammalian target of rapamycin kinase inhibition by rapamycin in glioblastoma. Clin Cancer Res 14:3416–3426

    Article  CAS  PubMed  Google Scholar 

  70. Wong ET, Hess KR, Gleason MJ, Jaeckle KA, Kyritsis AP, Prados MD, Levin VA, Yung WK (1999) Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol 17:2572–2578

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The Dr. Senckenberg Institute of Neurooncology is supported by the Dr. Senckenberg Foundation and the Hertie Foundation. JP Steinbach is Hertie Professor for Neurooncology. This work was supported within the Brain Tumor Network BTNplus (Subproject 10, Novel functions of BCL-2 family proteins in glioblastomas: invasiveness and autophagy) of the National Genome Research Network (NGFNplus) by the Federal Ministry of Education and Research (BMBF), and the Hertie Foundation.

Conflict of interest statement

Although the authors have not received and will not receive benefits for personal or professional use for a commercial party related directly or indirectly to the subject of this article, benefits have been or will be received but are directed solely to a research fund, foundation, educational institution or other non-profit organization with which one or more of the authors is/are associated.

Author information

Authors and Affiliations

  1. Dr. Senckenberg Institute of Neurooncology, Center of Neurology and Neurosurgery, Goethe-University Hospital, Schleusenweg 2–16, 60528, Frankfurt am Main, Germany

    Michael W. Ronellenfitsch & Joachim P. Steinbach

  2. Department of Neurooncology, Neurology Clinic and National Center for Tumor Disease, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    Wolfgang Wick

Authors
  1. Michael W. Ronellenfitsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joachim P. Steinbach
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wolfgang Wick
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael W. Ronellenfitsch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ronellenfitsch, M.W., Steinbach, J.P. & Wick, W. Epidermal growth factor receptor and mammalian target of rapamycin as therapeutic targets in malignant glioma: current clinical status and perspectives. Targ Oncol 5, 183–191 (2010). https://doi.org/10.1007/s11523-010-0154-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11523-010-0154-5

Keywords

Search

Navigation