Targeting Nuclear EGFR: Strategies for Improving Cetuximab Therapy in Lung Cancer

Abstract

Non-Small Cell Lung Cancer (NSCLC) is a deadly disease that is driven by a multitude of factors. One of these factors is the epidermal growth factor receptor (EGFR). One of the most prominent molecular targeting agents to the EGFR is the antibody cetuximab. However, most patients develop resistance to this antibody. We have found in models of cetuximab resistance that the EGFR changes its location, to the nucleus, where it is not accessible to the large antibody and can lead to resistance to cetuximab. Over the life of this grant we have found that 1) SFK, but not AKT, inhibition can block nuclear translocation, increase EGFR on the plasma membrane, 2) that blocking nuclear translocation of the EGFR via SFK blockade can overcome acquired resistance to cetuximab and 3) nEGFR is expressed in NSCLC, with a prevalence in SCC and that it is a predictive factor for PFS and OS.

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Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2015
Accession Number
AD1007281

Entities

People

  • Deric L Wheeler
  • Mari Iida

Organizations

  • University of Wisconsin–Madison

Tags

DTIC Thesaurus Topics

  • Biological Factors
  • Carcinoma
  • Cell Membrane
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Health Services
  • Medical Personnel
  • Oncology
  • Proteins

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