EGFR Signaling and Drug Discovery

  title={EGFR Signaling and Drug Discovery},
  author={Georg Lurje and Heinz-Josef Lenz},
  pages={400 - 410}
Dysregulation of human epidermal growth factor receptor (ErbB/HER) pathways by over-expression or constitutive activation can promote tumor processes including angiogenesis and metastasis and is associated with poor prognosis in many human malignancies. In addition to cancer, ErbB signaling has also been implicated in cardiovascular and neurodegenerative diseases. Conversely, inhibition of ErbB pathways with targeted agents, such as monoclonal antibodies (MoAbs) or tyrosine kinase inhibitors… 

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Recent major advances in the EGFR field include the discovery of EGFR somatic mutations in NSCLC that have important implications for biology, treatment, clinical trial design, and methods for mutation detection.
EGFR, HER2 and VEGF pathways: validated targets for cancer treatment.
Several targeted therapies with anti-tumour activity in human cancer cell lines and xenograft models have now been shown to produce objective responses, delay disease progression and, in some cases, improve survival of patients with advanced malignancies.
Rational bases for the development of EGFR inhibitors for cancer treatment.
Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody.
Why the epidermal growth factor receptor? The rationale for cancer therapy.
The rationale for EGFR-targeted approaches to cancer treatment is apparent and now well established, and there is increasing evidence that they may represent a significant contribution to cancer therapy.
Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells.
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Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy.
Inhibitory activity of cetuximab on epidermal growth factor receptor mutations in non–small cell lung cancers
Evaluating the effect of cetuximab on several NSCLC lines harboring some of the more common EGFR mutations, including L858R and delL747-T753insS, as well as the recently identified kinase inhibitor–resistant mutation, T790M showed that the kinase activity of the abovementioned EGFR mutants was hindered by cetUXimab, as detected by both cell-based phosphorylation and proliferation assays.
Epidermal growth factor receptor biology (IMC-C225)
IMC-C225, a novel monoclonal antibody that targets the EGFR, may prove to become a valuable contributor in the treatment of cancer.