Inhibiting Epidermal Growth Factor Receptor Dimerization and Signaling Through Targeted Delivery of a Juxtamembrane Domain Peptide Mimic.

ABSTRACT: Overexpression and deregulation of the epidermal growth factor receptor (EGFR) are implicated in multiple human cancers and therefore are a focus for the development of therapeutics. Current strategies aimed at inhibiting EGFR activity include monoclonal antibodies and tyrosine kinase inhibitors. However, activating mutations severely limit the efficacy of these therapeutics. There is thus a growing need for novel methods to inhibit EGFR. One promising approach involves blocking the association of the cytoplasmic juxtamembrane (JM) domain of EGFR, which has been shown to be essential for receptor dimerization and kinase function. Here, we aim to improve the selectivity and efficacy of an EGFR JM peptide mimic by utilizing the pH(low) insertion peptide (pHLIP), a unique molecule that can se

SUBMITTER: Gerhart J 

PROVIDER: S-EPMC6158778 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature