To design therapeutic approaches, researchers are examining the impact of the epidermal growth factor receptor (EGFR) on the development and prognosis of epithelial malignancies
[17][18]. EGFR has emerged as a critical target molecule for enhanced tumor specificity because of its diverse functional roles in cancer
[19]. EGFR is a transmembrane tyrosine kinase receptor with a molecular weight of 170 kDa that belongs to the ErbB family of cell membrane receptors. Other receptors in this family, in addition to EGFR (also known as HER1 and ErbB-1), include HER2/c-neu (ErbB-2), HER3 (ErbB-3), and HER4. (ErbB-4). All of these receptors have a cytoplasmic tyrosine kinase-containing domain, a single membrane-spanning region, and an extracellular ligand-binding region
[20]. In several malignancies, such as head and neck carcinomas, EGFR expression, which is normally assessed by immunohistochemistry, has been linked to tumor development and poor survival
[21]. However, the importance of EGFR protein expression in other cancers, such as lung carcinomas, remains controversial, as the level of EGFR overexpression may vary anywhere from 25 to 82% in colorectal cancers
[22].
In addition to EGFR expression levels, ligand binding to EGFR is important in functions that modulate various aspects of colorectal cancers. ADAM17 is a critical enzyme in the regulation of the release of EGFR ligands, which include EGF, amphiregulin, and heparin-binding EGF
[23]. Ligand binding to the extracellular domain phosphorylates the tyrosine kinase domain, activating signaling pathways involved in cell proliferation, angiogenesis, migration, continued existence, and adhesion. Since cancer cells rely on these pathways, EGFR is a useful target in the therapy of colorectal cancer metastases
[8]. EGF, transforming growth factor (TGF-), β-cellulin, epiregulin (EREG), epigen (EPGN), amphiregulin (AREG), and heparin-binding EGF are the most common EGFR ligands
[24]. Conventional EGFR activation begins when a ligand binds to the extracellular domain, inducing a conformational change that causes monomer EGFRs to dimerize
[25]. This brings cytoplasmic regions closer together, enabling autophosphorylation of tyrosine residues in the regulatory region. Autophosphorylated tyrosine residues function as anchors for various genes, including GRB2, SHC, SRC, and PI3K, which recruit and activate the RAS, AKT, and STAT signaling pathways, thereby initiating essential cellular processes
[26]. EGFR is often mutated in patients with solid tumors. Overexpression of the EGFR protein and kinase-activating mutations are the two forms of pathogenic EGFR changes found in cancer. The kinase-activating mutations that result in enhanced EGFR tyrosine kinase activity might occur as a result of, or in addition to, anti-EGFR therapy. While these markers can be useful tools in the diagnosis of colorectal cancer, current methods of diagnosis primarily use stool samples and colonoscopies
[27]. Colorectal cancer is currently diagnosed using stool samples and colonoscopies. The cancer is classified as either colonic or rectal, depending on its location. Both types of tumors exhibit obvious similarities; however, due to their differences in location, their molecular properties likewise differ. Treatment depends on the tumor’s response to chemotherapy or anti-EGFR monoclonal antibodies
[28].