EGFR: An essential receptor tyrosine kinase-regulator of cancer stem cells.

Abstract

The Epidermal Growth Factor Receptor (EGFR) is frequently expressed at elevated levels in different forms of cancer and expression often correlates positively with cancer progression and poor prognosis. Different mutant forms of this protein also contribute to cancer heterogeneity. A constitutively active form of EGFR, EGFRvIII is one of the most important variants. EGFR is responsible for the maintenance and functions of cancer stem cells (CSCs), including stemness, metabolism, immunomodulatory-activity, dormancy and therapy-resistance. EGFR regulates these pathways through several signaling cascades, and often cooperates with other RTKs to exert further control. Inhibitors of EGFR have been extensively studied and display some anticancer efficacy. However, CSCs can also acquire resistance to EGFR inhibitors making effective therapy even more difficult. To ameliorate this limitation of EGFR inhibitors when used as single agents, it may be of value to simultaneously combine multiple EGFR inhibitors or use EGFR inhibitors with regulators of other important cancer phenotype regulating molecules, such as STAT3, or involved in important processes such as DNA repair. These combinatorial approaches require further experimental confirmation, but if successful would expand and improve therapeutic outcomes employing EGFR inhibitors as one arm of the therapy.

• Authors: Sarmistha Talukdar, Luni Emdad, Swadesh K Das, Paul B Fisher
• Journal: Advances in cancer research (Adv Cancer Res) Vol. 147 Pg. 161-188 ( 2020) ISSN: 2162-5557 [Electronic] United States
• PMID: 32593400 (Publication Type: Journal Article, Review)
• Copyright: © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Protein Kinase Inhibitors
• ErbB Receptors

Topics

• Animals
• Disease Progression
• Drug Resistance, Neoplasm
• ErbB Receptors (antagonists & inhibitors, genetics, metabolism)
• Humans
• Molecular Targeted Therapy
• Mutation
• Neoplasms (drug therapy, enzymology, genetics, pathology)
• Neoplastic Stem Cells (drug effects, enzymology, pathology)
• Phosphorylation
• Protein Kinase Inhibitors (therapeutic use)
• Signal Transduction