298
Views
29
CrossRef citations to date
0
Altmetric
Theme: Nervous System Neoplasms - Review

A novel treatment for glioblastoma: integrin inhibition

, , &
Pages 421-435 | Published online: 09 Jan 2014

References

  • Wen PY, Kesari S. Malignant gliomas in adults. N. Engl. J. Med.359(5), 492–507 (2008).
  • Grossman SA, Ye X, Piantadosi S et al. Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States. Clin. Cancer Res.16(8), 2443–2449 (2010).
  • Moustakas A, Kreisl TN. New treatment options in the management of glioblastoma multiforme: a focus on bevacizumab. Oncol. Targets Ther.3, 27–38 (2010).
  • Parsons DW, Jones S, Zhang X et al. An integrated genomic analysis of human glioblastoma multiforme. Science321(5897), 1807–1812 (2008).
  • Lee SM, Koh HJ, Park DC, Song BJ, Huh TL, Park JW. Cytosolic NADP(+)-dependent isocitrate dehydrogenase status modulates oxidative damage to cells. Free Radic. Biol. Med.32(11), 1185–1196 (2002).
  • Kim SY, Lee SM, Tak JK, Choi KS, Kwon TK, Park JW. Regulation of singlet oxygen-induced apoptosis by cytosolic NADP(+)-dependent isocitrate dehydrogenase. Mol. Cell Biochem.302(1–2), 27–34 (2007).
  • Reardon DA, Rich JN, Friedman HS, Bigner DD. Recent advances in the treatment of malignant astrocytoma. J. Clin. Oncol.24(8), 1253–1265 (2006).
  • Bredel M, Scholtens DM, Yadav AK et al. NFKBIA deletion in glioblastomas. N. Engl. J. Med.364(7), 627–637 (2011).
  • Stupp R, Mason WP, van den Bent MJ et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med.352(10), 987–996 (2005).
  • Stupp R, Hegi ME, Mason WP et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised Phase 3 study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol.10(5), 459–466 (2009).
  • Yung WK, Prados MD, Yaya-Tur R et al. Multicenter Phase 2 trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse: temodal brain tumor group. J. Clin. Oncol.17(9), 2762–2771 (1999).
  • Wong ET, Hess KR, Gleason MJ et al. Outcomes and prognostic factors in recurrent glioma patients enrolled onto Phase 2 clinical trials. J. Clin. Oncol.17(8), 2572–2578 (1999).
  • Yung WK, Albright RE, Olson J et al. A Phase 2 study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Br. J. Cancer83(5), 588–593 (2000).
  • Perry JR, Bélanger K, Mason WP et al. Phase 2 trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study. J. Clin. Oncol.28(12), 2051–2057 (2010).
  • Wick A, Pascher C, Wick W et al. Rechallenge with temozolomide in patients with recurrent gliomas. J. Neurol.256(5), 734–741 (2009).
  • Friedman HS, Prados MD, Wen PY et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J. Clin. Oncol.27(28), 4733–4740 (2009).
  • Kreisl TN, Kim L, Moore K et al. Phase 2 trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J. Clin. Oncol.27(5), 740–745 (2009).
  • Folkman J. Angiogenesis: an organizing principle for drug discovery? Nat. Rev. Drug Discov.6(4), 273–286 (2007).
  • Dunn IF, Heese O, Black PM. Growth factors in glioma angiogenesis: FGFs, PDGF, EGF, and TGFs. J. Neuro. Oncol.50(1–2), 121–137 (2000).
  • Keunen O, Johansson M, Oudin A et al. Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma. Proc. Natl Acad. Sci.108(9), 3749–3754 (2011).
  • Norden AD, Young GS, Setayesh K et al. Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology70(10), 779–787 (2008).
  • Narayana A, Kunnakkat SD, Medabalmi P et al. Change in pattern of relapse after antiangiogenic therapy in high-grade glioma. Int. J. Radiat. Oncol. Biol. Phys.82(1), 77–82 (2012).
  • Chamberlain MC. Radiographic patterns of relapse in glioblastoma. J. Neuro. Oncol.101(2), 319–323 (2011).
  • Pope WB, Xia Q, Paton VE et al. Patterns of progression in patients with recurrent glioblastoma treated with bevacizumab. Neurology76(5), 432–437 (2011).
  • Wick A, Dörner N, Schäfer N et al. Bevacizumab does not increase the risk of remote relapse in malignant glioma. Ann. Neurol.69(3), 586–592 (2011).
  • Hanahan D, Weinberg R. The hallmarks of cancer. Cell100(1), 57–70 (2000).
  • Heddleston JM, Li Z, Hjelmeland AB, Rich AB. The hypoxic microenvironment maintains glioblastoma stem cells and promotes reprogramming towards a cancer stem cell phenotype. Cell Cycle8(20), 3274–3284 (2009).
  • Zhihong L, Wang H, Eyler CE, Hjelmeland AB, Rich JN. Turning cancer stem cells inside out: an exploration of glioma stem cell signaling pathways. J. Biol. Chem.284(25), 16705–16709 (2009).
  • Stupp R, Ruegg C. Integrin inhibitors reaching the clinic. J. Clin. Oncol.25(13), 1637–1638 (2007).
  • Lefranc F, Brotchi J, Kiss R. Possible future issues in the treatment of glioblastomas: special emphasis on cell migration and the resistance of migrating glioblastoma cells to apoptosis. J. Clin. Oncol.23(10), 2411–2422 (2005).
  • Folkman J. What is the evidence that tumors are angiogenesis dependent? J. Natl Cancer Inst.82(1), 4–6 (1990).
  • Ferrara N. Role of vascular endothelial growth factor in physiologic and pathologic angiogenesis: therapeutic implications. Semin. Oncol.29(6 Suppl. 16), 10–14 (2002).
  • Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell86(3), 353–364 (1996).
  • Folkman J. Is angiogenesis an organizing principle in biology and medicine? J. Pediatr. Surg.42(1), 1–11 (2007).
  • Kioi M, Vogel H, Schultz G, Hoffman RM, Harsh GR, Brown JM. Inhibition of vasculogenesis, but not angiogenesis, prevents the recurrence of glioblastoma after irradiation in mice. J. Clin. Invest.120(3), 694–705 (2010).
  • Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin. Oncol.29(6 Suppl. 16), 15–18 (2002).
  • Reardon DA, Neyns B, Weller M, Tonn JC, Nabors LB, Stupp R. Cilengitide: an RGD-pentapeptide αVβ3 and αVβ5 integrin inhibitor in development for glioblastoma and other malignancies. Future Oncol.7(3), 339–354 (2011).
  • Ruoslahti E. RGD and other recognition sequences for integrins. Annu. Rev. Cell Dev. Biol.12, 697–715 (1996).
  • Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell110(6), 673–687 (2002).
  • Legate KR, Wickstrom SA, Fassler R. Genetic and cell biological analysis of integrin outside-in signaling. Genes Dev.23(4), 397–418 (2009).
  • Contois L, Akalu A, Brooks PC. Integrins as ‘functional hubs’ in the regulation of pathological angiogenesis. Semin. Cancer Biol.19(5), 318–328 (2009).
  • Desgrosellier JS, Cheresh DA. Integrins in cancer: biological implications and therapeutic opportunities. Nat. Rev. Cancer10(1), 9–22 (2010).
  • Baker EL, Zaman MH. The biomechanical integrin. J. Biomechanics43(1), 38–44 (2010).
  • Jin H, Aiyer A, Su J. A homing mechanism for bone marrow-derived progenitor cell recruitment to the neovasculature. J. Clin. Invest.116(3), 652–662 (2006).
  • Avraamides CJ, Garmy-Susini B, Varner JA. Integrins in angiogenesis and lymphangiogenesis. Nat. Rev. Cancer8(8), 604–617 (2008).
  • Garmy-Susini B, Jin H, Zhu Y, Sung RJ, Hwang R, Varner J. Integrin α4β1-VCAM-1-mediated adhesion between endothelial and mural cells is required for blood vessel maturation. J. Clin. Invest.115(6), 1542–1551 (2005).
  • Trikha M, Zhou Z, Timar J et al. Multiple roles for platelet GPIIb/IIIa and αVβ3 integrins in tumor growth, angiogenesis, and metastasis. Cancer Res.62(10), 2824–2833 (2002).
  • Bello L, Francolini M, Marthyn P et al. αVβ3 and αVβ5 integrin expression in glioma periphery. Neurosurgery49(2), 380–389 (2001).
  • Schnell O, Krebs B, Wagner E. Expression of integrin αVβ3 in gliomas correlates with tumor grade and is not restricted to tumor vasculature. Brain Pathol.18(3), 378–386 (2008).
  • Paulus W, Baur I, Schuppan D, Roggwendorf W. Characterization of integrin receptors in normal and neoplastic human brain. Am. J. Pathol.143, 154–163 (1993).
  • Rutka JT, Muller M, Hubbard SL et al. Astrocytoma adhesion to extracellular matrix: functional significance of integrin and focal adhesion kinase expression. J. Neuropathol. Exp. Neurol.58(2), 198–209 (1999).
  • Belot N, Rorive S, Doyen I et al. Molecular characterization of cell substratum attachments in human glial tumors relates to prognostic features. Glia36(3), 375–390 (2001).
  • Taga T, Suzuki A, Gonzalez-Gomez I et al. αv-integrin antagonist EMD 121974 induces apoptosis in brain tumor cells growing on vitronectin and tenascin. Int. J. Cancer98(5), 690–697 (2002).
  • Galli R, Binda E, Orfanelli U. Isolation and characterization of tumorigenic, stem-like neural precursors from human glioglastoma. Cancer Res.64(11), 7011–7021 (2004).
  • Singh SK, Hawkins C, Clarke ID. Identification of human brain tumour initiating cells. Nature432(7015), 396–401 (2004).
  • Schmalz PGR, Shen MJ, Park JK. Treatment resistance mechanisms of malignant glioma tumor stem cells. Cancers3(1), 621–635 (2011).
  • Li Z, Wang H, Eyler CE, Hjelmeland AB, Rich JN. Turning cancer stem cells inside out: an exploration of glioma stem cell signaling pathways. J. Biol. Chem.284(25), 16705–16709 (2009).
  • Lathia JD, Gallagher J, Heddleston JM et al. Integrin α6 regulates glioblastoma stem cells. Cell Stem Cell6(5), 421–432 (2010).
  • Skuli N, Monferran S, Delmas C et al. αVβ3/αVβ5 integrins–FAK–RhoB: a novel pathway for hypoxia regulation in glioblastoma. Cancer Res.69(8), 3308–3316 (2009).
  • Kaur B, Khwaja FW, Severson EA, Matheny SL, Brat DJ, Van Meir EG. Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis. Neuro. Oncol.7(2), 134–153 (2005).
  • Maxwell PH, Pugh CW, Ratcliffe PJ. Activation of the HIF pathway in cancer. Curr. Opin. Genet. Dev.11(3), 293–299 (2001).
  • Semenza GL. HIF-1: mediator of physiological and pathophysiological responses to hypoxia. J. Appl. Physiol.88(4), 1474–1480 (2000).
  • Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway. J. Clin. Oncol.23(5), 1011–1027 (2005).
  • Millard M, Odde S, Neamati N. Integrin targeted therapeutics. Theranostics1, 154–188 (2011).
  • Abdollahi A, Lipson KE, Sckell A et al. Combined therapy with direct and indirect angiogenesis inhibition results in enhanced antiangiogenic and antitumor effects. Cancer Res.63(24), 8890–8898 (2003).
  • McNeel DG, Eickhoff J, Lee FT et al. Phase 1 trial of a monoclonal antibody specific for αVβ3 integrin (MEDI-522) in patients with advanced malignancies, including an assessment of effect on tumor perfusion. Clin. Cancer Res.11(21), 7851–7860 (2005).
  • Mullamitha SA, Ton NC, Parker GJ et al. Phase 1 evaluation of a fully human anti-αV integrin monoclonal antibody (CNTO 95) in patients with advanced solid tumors. Clin. Cancer Res.13(7), 2128–2135 (2007).
  • Ricart AD, Tolcher AW, Liu G et al. Volociximab, a chimeric monoclonal antibody that specifically binds α5β1 integrin: a Phase 1, pharmacokinetic, and biological correlative study. Clin. Cancer Res.14(23), 7924–7929 (2008).
  • Mas-Moruno C, Rechenmacher F, Kessler H. Cilengitide: the first anti-angiogenic small molecule drug candidate. Design, synthesis and clinical evaluation. Anticancer Agents Med. Chem.10(10), 753–768 (2010).
  • Loges S, Butzal M, Otten J. Cilengitide inhibits proliferation and differentiation of human endothelial progenitor cells in vitro. Biochem. Biophys. Res. Commun.357(4), 1016–1020 (2007).
  • Albert JM, Cao C, Geng L, Leavitt L, Hallahan DE, Lu B. Integrin αVβ3 antagonist cilengitide enhances efficacy of radiotherapy in endothelial cell and non-small cell lung cancer models. Int. J. Radiat. Oncol. Biol. Phys.65(5), 1536–1543 (2006).
  • Mikkelsen T, Brodie C, Finniss S et al. Radiation sensitization of glioblastoma by cilengitide has unanticipated schedule-dependency. Int. J. Cancer124(11), 2719–2727 (2009).
  • Reynolds AR, Hart IR, Watson AR et al. Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors. Nat. Med.15(4), 392–400 (2009).
  • Dechantsreiter MA, Planker E, Mathä B et al. N-methylated cyclic RGD peptides as highly active and selective αVβ3 integrin antagonists. J. Med. Chem.42(16), 3033–3040 (1999).
  • Nisato RE, Tille JC, Jonczyk A et al. αVβ3 and αVβ5 integrin antagonists inhibit angiogenesis in vitro. Angiogenesis6(2), 105–119 (2003).
  • Xiong JP, Stehle T, Zhang R et al. Crystal structure of the extracellular segment of integrin αvβ3. Science296(5565), 151–155 (2002).
  • Friedlander M, Brooks PC, Shaffer RW, Kincaid CM, Varner JA, Cheresh DA. Definition of two angiogenic pathways by distinct αV integrins. Science270(5241), 1500–1502 (1995).
  • Hammes HP, Brownlee M, Jonczyk A, Sutter A, Preissner KT. Subcutaneous injection of a cyclic peptide antagonist of vitronectin receptor-type integrins inhibits retinal neovascularization. Nat. Med.2(5), 529–533 (1996).
  • Yamada S, Bu XY, Khankaldyyan V, Gonzales-Gomez I, McComb JG, Laug WE. Effect of the angiogenesis inhibitor cilengitide (EMD 121974) on glioblastoma growth in nude mice. Neurosurgery59(6), 1304–1312 (2006).
  • Tentori L, Dorio AS, Muzi A et al. The integrin antagonist cilengitide increases the antitumor activity of temozolomide against malignant melanoma. Oncol. Rep.19(4), 1039–1043 (2008).
  • Lode HN, Moehler T, Xiang R et al. Synergy between an anti-angiogenic integrin αV antagonist and an antibody-cytokine fusion protein eradicates spontaneous tumor metastases. Proc. Natl Acad. Sci.96(4), 1591–1596 (1999).
  • Eskens FA, Dumez H, Hoekstra R et al. Phase 1 and pharmacokinetic study of continuous twice weekly intravenous administration of cilengitide (EMD 121974), a novel inhibitor of the integrins αVβ3 and αVβ5 in patients with advanced solid tumours. Eur. J. Cancer39(7), 917–926 (2003).
  • Nabors LB, Mikkelsen T, Rosenfeld SS et al. Phase 1 and correlative biology study of cilengitide in patients with recurrent malignant glioma. J. Clin. Oncol.25(13), 1651–1657 (2007).
  • MacDonald TJ, Stewart CF, Kocak M et al. Phase 1 clinical trial of cilengitide in children with refractory brain tumors: Pediatric Brain Tumor Consortium study PBTC-012. J. Clin. Oncol.26(6), 919–924 (2008).
  • Lam MSH, Ignoffo RJ. A guide to clinically relevant drug interactions in oncology. J. Oncol. Pharm. Pract.9, 45–85 (2003).
  • Rubenstein JL, Kim J, Ozawa T et al. Anti-VEGF antibody treatment of glioblastoma prolongs survival but results in increased vascular cooption. Neoplasia2(4), 306–314 (2000).
  • Batchelor TT, Duda DG, di Tomaso E et al. Phase 2 study of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. J. Clin. Oncol.28(17), 2817–2823 (2010).
  • Reardon DA, Fink KL, Mikkelsen T et al. Randomized Phase 2 study of cilengitide, an integrin-targeting arginine-lysine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme. J. Clin. Oncol.26(34), 5610–5617 (2008).
  • Fink K, Mikkelsen T, Nabors LB et al. Long-term effects of cilengitide, a novel integrin inhibitor, in recurrent glioblastoma: a randomized Phase 2a study. J. Clin. Oncol.28(Suppl. 15), (2010) (Abstract 2010).
  • Gilbert M, Lamborn K, Lassman AB et al. Tumor tissue delivery of cilengitide after intravenous administration to patients with recurrent glioblastoma (GBM): preliminary data from NABTC protocol 03-02. Presented at: The 12th Annual Meeting of the Society for Neuro-Oncology. Dallas, TX, USA, 15–18 November 2007.
  • Stupp R, Hegi ME, Neyns B et al. Phase 1/2a study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosed glioblastoma. J. Clin. Oncol.28(16), 2712–2718 (2010).
  • Hegi ME, Diserens AC, Gorlia T et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N. Engl. J. Med.352(10), 997–1003 (2005).
  • Verhaak RGW, Hoadley KA, Purdom E et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell17(1), 98–110 (2010).
  • Nabors LB, Mikkelsen T, Batchelor T et al. NABTT 0306: a randomized Phase 2 trial of EMD 121974 in conjunction with concomitant and adjuvant temozolomide with radiation therapy in patients with newly diagnosed glioblastoma multiforme (GBM). J. Clin. Oncol.27, S15 (2009) (Abstract 2001).
  • Franceschi E, Tosoni A, Bartolini S, Mazzocchi V, Fioravanti A, Brandes AA. Treatment options for recurrent glioblastoma: pitfalls and future trends. Expert Rev. Anticancer Ther.9(5), 613–619 (2009).
  • Galanis E, Buckner JC, Maurer MJ et al. Phase 2 trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: a North Central Cancer Treatment group study. J. Clin. Oncol.23(23), 5294–5304 (2005).
  • Stupp R, Van Den Bent J, Erridge SC et al. Cilengitide in newly diagnosed glioblastoma with MGMT promoter methylation: protocol of a multicenter, randomized, open-label, controlled Phase 2 trial (CENTRIC). J. Clin. Oncol.28(Suppl. 15), (2010) (Abstract TPS152).
  • Grossman SA, Ye X, Chamberlain M et al. Talampanel with standard radiation and temozolomide in patients with newly diagnosed glioblastoma: a multicenter Phase 2 trial. J. Clin. Oncol.27(25), 4155–4161 (2009).
  • Rosenfeld MR, Chamberlain MC, Grossman SA et al. A multi-institution Phase 2 study of poly-ICLC and radiotherapy with concurrent and adjuvant temozolomide in adults with newly diagnosed glioblastoma. Neuro. Oncol.12(10), 1071–1077 (2010).
  • Avastin ®, package insert. Genentech, Inc., CA, USA (2011).

Websites

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.