Epidermal growth factor receptor (EGFR) involvement in epithelial-derived cancers and its current antibody-based immunotherapies

Cell Biol Int. 2020 Jun;44(6):1267-1282. doi: 10.1002/cbin.11340. Epub 2020 Mar 17.

Abstract

The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein that is part of the family of tyrosine kinase receptors. The binding of EGFR to its cognate ligands leads to its autophosphorylation and subsequent activation of the signal transduction pathways involved in regulating cellular proliferation, differentiation, and survival. Accordingly, this receptor carries out both redundant and restricted functions in the germline development of mammals and in the maintenance of various adult tissues. Correspondingly, the loss of EGFR regulation results in many human diseases, with the most notable cancer. This receptor is overexpressed and/or mutated in multiple epithelial-derived tumors, and associated with poor prognosis and survival in cancer patients. Here, we discuss in detail the role of EGFR in specific epithelial-derived cancer pathologies; these include lung cancer, colorectal cancer, and squamous cell carcinomas. The development of multiple anticancer agents against EGFR diminished the progression and metastasis of tumors. Some of the most versatile therapeutic anti-EGFR agents include the monoclonal antibodies (mAbs), demonstrating success in clinical settings when used in combination with cytotoxic treatments, such as chemotherapy and/or radiation. We thus discuss the development and application of two of the most notable therapeutic mAbs, cetuximab, and panitumumab, currently utilized in various EGFR-related epithelial cancers.

Keywords: antibody therapeutics; cancer therapeutics; epidermal growth factor receptor; oncology; receptor tyrosine kinase.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Squamous Cell* / drug therapy
  • Carcinoma, Squamous Cell* / metabolism
  • Cetuximab / therapeutic use
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / metabolism
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Humans
  • Immunotherapy
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / metabolism
  • Panitumumab / therapeutic use

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Panitumumab
  • EGFR protein, human
  • ErbB Receptors
  • Cetuximab

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