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A Rational Approach to Target the Epidermal Growth Factor Receptor in Glioblastomas.


Posted on: 12/31/2016

  Curr Cancer Drug Targets. 2016 Dec 26. [Epub ahead of print]
A Rational Approach to Target the Epidermal Growth Factor Receptor in Glioblastomas.
Kwatra MM1.
 
Author information:
1Departments of Anesthesiology, Pharmacology, and Cancer Biology, Duke University Medical Center, Durham, NC 27705, USA.
 
Abstract
 
Glioblastoma (GBM) is a deadly brain cancer, and all attempts to control it have failed so far. However, the future looks bright, as we now know the molecular landscape of GBM through the work of The Cancer Genome Atlas (TCGA) program. GBMs exhibit significant inter- and intra-tumoral heterogeneity, and to control this type of tumor, a personalized approach is required. One target, whose gene is amplified and mutated in a large number of GBMs, is the epidermal growth factor receptor (EGFR). But all attempts to target it have been unsuccessful. We attribute the reason for this failure to the molecular heterogeneity of EGFR in GBM, as well as to the poor brain penetration of previously tested EGFR-Tyrosine Kinase Inhibitors (EGFR-TKIs). In this review, we discuss the molecular heterogeneity of EGFR and provide rational preclinical and clinical guidelines for testing AZD9291, a third generation, irreversible EGFR-TKI with both a high affinity for EGFRvIII and excellent brain penetration.
PMID: 28029074 [PubMed - as supplied by publisher]

 


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