Targeting the Epidermal Growth Factor Receptor in Solid Tumor Malignancies

Abstract

The epidermal growth factor receptor (EGFR) is over-expressed, as well as mutated, in many types of cancers. In particular, the EGFR variant type III mutant (EGFRvIII) has attracted much attention as it is frequently and exclusively found on many tumor cells, and hence both EGFR and EGFRvIII have been proposed as valid targets in many cancer therapy settings. Different strategies have been developed in order to either inhibit EGFR/EGFRvIII activity or to ablate EGFR/EGFRvIII-positive tumor cells. Drugs that inhibit these receptors include monoclonal antibodies (mAbs) that bind to the extracellular part of EGFR, blocking the binding sites for the EGFR ligands, and intracellular tyrosine kinase inhibitors (TKIs) that block the ATP binding site of the tyrosine kinase domain. Besides an EGFRvIII-targeted vaccine, conjugated anti-EGFR mAbs have been used in different settings to deliver lethal agents to the EGFR/EGFRvIII-positive cells; among these are radio-labelled mAbs and immunotoxins. This article reviews the current status and efficacy of EGFR/EGFRvIII-targeted therapies.

Systematic identification of personal tumor-specific neoantigens in chronic lymphocytic leukemia

“…[1][2][3][4] Past cancer vaccine efforts have lacked efficacy that may stem from their focus on overexpressed or selectively expressed tumor-associated native antigens as vaccine targets that require overcoming the challenging hurdles of breaking central and peripheral tolerance while risking the generation of autoimmunity. [4][5][6] The rare examples of successful cancer vaccines in humans have targeted foreign pathogen-associated antigens 7 or a mutated growth factor receptor 8 or are idiotype vaccines derived from patient-specific rearranged immunoglobulins. 9 These studies point to the importance of selecting immunogens distinct from self, where central/peripheral tolerance can be overcome and the risk of autoimmunity is minimal.…”

The Immunogenicity and Anti-Tumor Efficacy of a Rationally Designed EGFR Vaccine

“…The ECD of mouse EGFR is responsible for ligand binding and the receptor dimerization, and is composed of four structural sub-domains, among which the sub-domain II (aa190-334) is responsible for the receptor dimerization, and the sub-domain III (aa335-506) is responsible for the ligand-binding [15]. The sub-domain III possesses two partially overlapping epitopes recognized respectively by anti-tumor monoclonal antibodies Cetuximab and Panitumab.…”

Growth factor pathways in hypertrophic scars: Molecular pathogenesis and therapeutic implications

“…However, little is known about the precise role of EGF in the advanced stage of hypertrophic scars. Given the well-established cancerogenic role of EGF [79] and its vague coordination with TGF-b signaling [71,72,80], whether EGF could alleviate or aggravate the progression of hypertrophic scars should be carefully examined in more reliable cellular and animal models over coming years.…”