Targeting Nuclear EGFR: Strategies for Improving Cetuximab Therapy in Lung Cancer
Technical Report,01 Sep 2012,31 Aug 2015
University of Wisconsin, Madison Madison United States
Pagination or Media Count:
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.