Epidermal Growth Factor Receptor: Key to Selective Intracellular Delivery

Abstract

Epidermal growth factor receptor (EGFR) is an integral surface protein mediating cellular response to a number of growth factors. Its overexpression and increased activation due to mutations is one of the most common traits of many types of cancer. Development and clinical use of the agents, which block EGFR activation, became a prime example of the personalized targeted medicine. However, despite the obvious success in this area, cancer cure remains unattainable in most cases. Because of that, as well as the result of the search for possible ways to overcome the difficulties of treatment, a huge number of new treatment methods relying on the use of EGFR overexpression and its changes to destroy cancer cells. Modern data on the structure, functioning, and intracellular transport of EGFR, its natural ligands, as well as signaling cascades triggered by the EGFR activation, peculiarities of the EGFR expression and activation in oncological disorders, as well as applied therapeutic approaches aimed at blocking EGFR signaling pathway are summarized and analyzed in this review. Approaches to the targeted delivery of various chemotherapeutic agents, radionuclides, immunotoxins, photosensitizers, as well as the prospects for gene therapy aimed at cancer cells with EGFR overexpression are reviewed in detail. It should be noted that increasing attention is being paid nowadays to the development of multifunctional systems, either carrying several different active agents, or possessing several environment-dependent transport functions. Potentials of the systems based on receptor-mediated endocytosis of EGFR and their possible advantages and limitations are discussed.

Evaluating the Expression and Prognostic Value of Genes Encoding Microtubule-Associated Proteins in Lung Cancer

“…Additionally, EGFR amplification was found to be correlated with increased expression of KIF4A and KIF18B , while EGFR mutation was related to the decreased expression of KIF18B in LUSC. Since EGFR initiates signal transduction through a network of downstream pathways that activate transcription of target genes [ 67 ], such as signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated kinase (ERK), and mTOR, it might indirectly regulate KIF4A and KIF18B transcription via these pathways. In addition, the multivariate analysis suggested that KIF18B was an independent predictor of OS in LUAD.…”

Mechanisms of Natural Extracts of Andrographis paniculata That Target Lipid-Dependent Cancer Pathways: A View from the Signaling Pathway

“…EGF and TGFα are the endogenous ligands for EGFR. As such, EGFR binds to its ligands [ 42 ]. EGFR dimerizes with another EGFR and autophosphorylates following ligand binding, which results in a sequence of intracellular signaling events.…”

Emerging Molecular Receptors for the Specific-Target Delivery of Ruthenium and Gold Complexes into Cancer Cells

“…The EGFR signaling network plays a primary role in the growth, maintenance, and homeostasis of epithelial tissues [ 82 , 83 ]. Many different types of cancer (e.g., lung, colorectal, pancreatic, breast, ovarian, cervical, bladder, neuroendocrine, glioma head, and neck) are associated with abnormalities in the EGFR axis, either by receptor overexpression, disfunction due to mutations, and/or increased autocrine and paracrine production of its growth factors [ 82 , 83 ]. Consequently, a huge number of anticancer drugs targeting EGFR are under clinical use or development, an approach that became a prime example of personalized targeted medicine [ 82 ].…”

“…Consequently, a huge number of anticancer drugs targeting EGFR are under clinical use or development, an approach that became a prime example of personalized targeted medicine [ 82 ]. Furthermore, EGFR can mediate the endocytosis of external agents into cancer cells, as well as translocate to the nucleus and the mitochondria, for which these receptors have been intensively studied as targets for the delivery of several chemotherapeutic, radionuclides, immunotoxins, and photosensitizers [ 83 ].…”