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 intratumoral 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.
Keywords: Glioblastoma, EGFR, heterogeneity, targeted, therapies, TCGA.
Current Cancer Drug Targets
Title:A Rational Approach to Target the Epidermal Growth Factor Receptor in Glioblastoma
Volume: 17 Issue: 3
Author(s): Madan M. Kwatra
Affiliation:
Keywords: Glioblastoma, EGFR, heterogeneity, targeted, therapies, TCGA.
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 intratumoral 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.
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Cite this article as:
Kwatra M. Madan, A Rational Approach to Target the Epidermal Growth Factor Receptor in Glioblastoma, Current Cancer Drug Targets 2017; 17 (3) . https://dx.doi.org/10.2174/1568009616666161227091522
DOI https://dx.doi.org/10.2174/1568009616666161227091522 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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