Epidermal Growth Factor Receptor: Key to Selective Intracellular Delivery
- PDF / 1,723,079 Bytes
- 27 Pages / 612 x 792 pts (letter) Page_size
- 14 Downloads / 227 Views
REVIEW
Epidermal Growth Factor Receptor: Key to Selective Intracellular Delivery A. A. Rosenkranz1,2,a* and T. A. Slastnikova2 1
Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia a email: [email protected]
2
Received June 15, 2020 Revised July 23, 2020 Accepted July 23, 2020 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 cas cades 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, photosensi tizers, 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 car rying several different active agents, or possessing several environmentdependent transport functions. Potentials of the sys tems based on receptormediated endocytosis of EGFR and their possible advantages and limitations are discussed. DOI: 10.1134/S0006297920090011 Key words: epidermal growth factor receptor, overexpression, endocytosis, cancer, targeted cancer therapy, drug delivery
INTRODUCTION Epidermal growth factor receptor (EGFR) is among one of the most studied proteins so that nearly 100,000 scientific publications are available in the PubMed data base describing investigation of its structure and proper ties as well as functioning in norm and pathology. Despite that, multiple aspects of its involvement in regulation of the processes occurring in an organism remain poorly understood, whereas steadily increasing set of com Abbreviations: AEs, Auger electrons; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; ER, endo plasmic reticulum; ErbB, avian erythroblastic leukemia viral (verbb) oncogene homolog (synonym: EGFR/HER); mAb, monoclonal antibody; MNTs, modular nanotransporters; PDT, photodynamic therapy; PEG, polyethylene glycol; PLGA, poly lacticcoglycolic acid; PRMT1
Data Loading...
