EGFRvIII-mediated radioresistance through a strong cytoprotective response

Inhibition of the Type III Epidermal Growth Factor Receptor Variant Mutant Receptor by Dominant-Negative EGFR-CD533 Enhances Malignant Glioma Cell Radiosensitivity

“…CHO cells were routinely seeded at 1.5 ϫ 10 5 cells per 60-mm dish. On day 3, transient transfections were performed at Ͼ80% efficiency with LipofectAMINE plus (GIBCO-BRL, Gaithersburg, MD) and 0.5 g of the ph␤Ac.EGFRvIII expression plasmid and 1.5 g of an empty vector DNA (20). Western blot analyses verified detectable expression of the ph␤Ac.…”

“…1D; P Ͻ 0.01), a response similar to the average 2.1-fold radiation-induced activation of EGFRwt. Considering the high constitutive activity of EGFRvIII (20), the mutant receptor, in addition to EGFRwt, is likely to represent an important modulator of radiation responses when tumor xenografts are irradiated.…”

“…The constitutively active EGFRvIII is prominently activated by radiation, but not by growth factors (20). It is widely expressed in vivo when human tumor cells are propagated as xenograft tumors, but expression is quickly lost on in vitro cultivation of tumor cells.…”

Stimulated PI3K-AKT Signaling Mediated through Ligand or Radiation-Induced EGFR Depends Indirectly, but not Directly, on Constitutive K-Ras Activity

“…This mechanism may also play a role in radioresistance of RAS-mutated tumors. Moreover, experimental and clinical evidence exists that overexpression or mutation of EGFR mediates tumor resistance to both chemotherapy and especially radiotherapy (18)(19)(20)(21)(22)(23), and EGFR overexpression has been correlated with accelerated repopulation of tumors undergoing radiotherapy (24).…”

Searching for a cure: Gene therapy for glioblastoma

“…In this regard, expression of a non-replicative type V recombinant adenovirus to express a dominant negative ERBB1 protein has been shown in vitro and in a flank xenograft tumor model system to slow the growth and to radiosensitize genetically modified human GBM cells expressing ERBB1 vIII. 96 Other approaches to this problem have included conjugation of siRNA molecules to knock down ERBB1 vIII expression to cetuximab as an approach to inhibit this receptor. 97 Whether a conditionally replicative version of the virus to express a dominant negative form of ERBB1 or a soluble form of the extracellular domain of ERBB1 to bind activating ligands could act as a GBM therapeutic has not yet been explored.…”