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. 2013 Jul 24:6:931-42.
doi: 10.2147/OTT.S33532. Print 2013.

Nimotuzumab as a radiosensitizing agent in the treatment of high grade glioma: challenges and opportunities

Arlhee Diaz-Miqueli  1 , Giselle Saurez Martinez
Affiliations

Nimotuzumab as a radiosensitizing agent in the treatment of high grade glioma: challenges and opportunities

Arlhee Diaz-Miqueli et al. Onco Targets Ther. .

Abstract

Nimotuzumab is a humanized monoclonal antibody that binds specifically to human epidermal growth factor receptor, blocking receptor activation. Evidence of its radiosensitizing capacity has been widely evaluated. This article integrates published research findings regarding the role of nimotuzumab in the treatment of high grade glioma in combination with radiotherapy or radiochemotherapy in adult and pediatric populations. First, the mechanisms of action of nimotuzumab and its current applications in clinical trials containing both radiation and chemoradiation therapies are reviewed. Second, a comprehensive explanation of potential mechanisms driving radiosensitization by nimotuzumab in experimental settings is given. Finally, future directions of epidermal growth factor receptor targeting with nimotuzumab in combination with radiation containing regimens, based on its favorable toxicity profile, are proposed. It is hoped that this review may provide further insight into the rational design of new approaches employing nimotuzumab as a useful alternative for the therapeutic management of high grade glioma.

Keywords: high grade gliomas; nimotuzumab; radiation.

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Figures

Figure 1
Figure 1
Simplified schematic illustration depicting different mechanisms implicated in radiosensitization by the anti-epidermal growth factor receptor monoclonal antibody nimotuzumab in high grade glioma. Notes: After ligand binding, tyrosine phosphorylation of tyrosine kinase domains may initiate signaling events or provide docking sites for adaptor molecules, including the SH2 domain containing proteins Shc and Grb, which in turn promotes the activation of multiple intracellular kinases, such as extracellular signal-regulated kinase (ERK) 1/2. The activation of ERK 1/2 leads to increased cell proliferation. The exposure of tumor cells to ionizing radiation may also increase epidermal growth factor receptor (EGFR) phosphorylation and activation of mitogen activated protein kinase (arrows shaded in green) and other related pathways. Nimotuzumab binds to the extracellular domain of the EGFR inhibiting receptor phosphorylation and ERK 1/2 activation, which results in inhibition of cell proliferation. Nimotuzumab also decreases angiogenic processes, probably by inhibiting the secretion of vascular endothelial growth factor type A by tumor cells (dashed arrows shaded in red). In addition, nimotuzumab induces G0/G1 cell cycle arrest, that in combination with radiation induced G2/M cell cycle arrest, might lead to increased apoptosis of tumor cells. Abbreviations: Akt, protein kinase B; CD, cluster differentiation; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; ERK, extracellular signal-regulated kinase; Grb2, growth factor receptor-bound protein 2; GTP, guanosine-5′-triphosphate; MEK, mitogen activated protein kinase kinase; mTOR, mammalian target of rapamycin; PI3K, phosphatidyl inositol 3 kinase; PIP2, phosphatidylinositol 4,5-bisphosphate; PIP3, phosphatidylinositol 3,4,5-trisphosphate; Raf, rapidly accelerated fibrosarcoma; Ras, rat sarcoma; SH2, Src homology-2; shc, Src-homology collagen protein; SOS, son of sevenless homolog 1; Src, sarcoma; STAT, signal transducer and activator of transcription; TGF-α, transforming growth factor alpha; VEGFA, vascular endothelial growth factor type A; VEGFR2, VEGF receptor 2.
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References

    1. Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114:97–109. - PMC - PubMed
    1. Laperriere N, Zuraw L, Cairncross G. Radiotherapy for newly diagnosed malignant glioma in adults: a systematic review. Radiother Oncol. 2002;64:259–273. - PubMed
    1. Hart MG, Grant R, Garside R, Rogers G, Somerville M, Stein K. Temozolomide for high grade glioma [review] Cochrane Database Syst Rev. 2008:CD007415. - PubMed
    1. Koshy M, Villano JL, Dolecek TA, et al. Improved survival time trends for glioblastoma using the SEER 17 population-based registries. J Neurooncol. 2012;107:207–212. - PMC - PubMed
    1. Nazzaro JM, Neuwelt EA. The role of surgery in the management of supratentorial intermediate and high-grade astrocytomas in adults. J Neurosurg. 1990;73:331–344. - PubMed