Profile of nimotuzumab in the treatment of high-grade glioma

Abstract

High-grade gliomas (HGG) are extremely aggressive lesions and represent the most common primary malignant brain tumors without an effective therapy. Standard treatment for HGG usually includes surgery followed by radiotherapy and chemotherapy. However, the prognosis of patients with HGG remains dismal. We review the humanized epidermal growth factor receptor (EGFR) and the major EGFR target drugs in HGG treatments, focusing on the EGFR antibody nimotuzumab as a new therapeutic strategy in HGG. We found that nimotuzumab with or without radiotherapy, chemotherapy in newly diagnosed or recurrent HGG, such as glioblastoma multiforme (GBM), anaplastic astrocytomas (AA), and diffuse intrinsic pontine glioma (DIPG), might improve the response rate or the survival time. In conclusion, nimotuzumab is a very well-tolerated drug with acceptable toxicity, and it may have promising value in the combination treatment. As a result, multiple center randomized controlled Phase III clinical trials need to be conducted to confirm the efficacy and toxicity for nimotuzumab in HGG.

Keywords: chemotherapy; high-grade gliomas; nimotuzumab; radiotherapy.

Figure 1

Simplified schematic illustration depicting different mechanisms implicated in radiosensitization by the antiepidermal growth factor receptor monoclonal antibody nimotuzumab in high-grade glioma. Note: Copyright © 2015. Dove Medical Press. Reproduced from Diaz-Miqueli A, Martinez GS. Nimotuzumab as a radiosensitizing agent in the treatment of high grade glioma: challenges and opportunities. Oncology Targets Therapy. 2013;6:931–942. 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.