Constitutive activation of the EGFR is common in cancer due to EGFR wild type (EGFRwt) overexpression or the presence of mutant EGFR. Signaling by constitutively active NSCLC EGFR mutants or the EGFRvIII mutant in glioblastoma has been studied intensively and the downstream signals are known. Normally, the EGFRwt is activated when it is exposed to ligand resulting in activation of canonical signals such as ERK and Akt. The EGFRwt also becomes tyrosine phosphorylated and constitutively activated without ligand when it is overexpressed, but downstream signals are unclear. Recent studies have identified a non-canonical form of signaling triggered by EGFRwt exclusively in the absence of ligand that does not involve ERK or Akt activation but, instead, results in activation of the transcription factor IRF3. Addition of ligand turns off IRF3 dependent transcription and activates ERK and Akt. Thus, the EGFR triggers distinct and mutually exclusive signaling networks depending on the presence of ligand. Furthermore, non-canonical EGFRwt signaling may influence response to treatment in cancer. Also, there are reports of both synergistic and antagonistic interactions between ligand-dependent EGFRwt and EGFRvIII signaling, Here, we discuss ligand-independent EGFR signal transduction by oncogenic EGFR mutants and EGFRwt, and review the interplay between EGFRwt and EGFRvIII.

The treatment of very large or giant unruptured intracranial aneurysms is hazardous and complex and thus best performed only at major cerebrovascular centers with an experienced team of neurosurgeons, interventional neuroradiologists, neurologists, and neuroanesthesiologists. Surgery, with acceptable risks and excellent occlusion rates, is typically the treatment of choice in patients younger than 50 years of age. In older patients, the benefits of endovascular treatment versus surgery versus no treatment must be carefully weighed individually. Minimizing temporary occlusion and the consequent use of intraoperative angiography may help reduce surgical complications.

No abstract

No abstract