EGFR (Epithelial Growth Factor Receptor) antibodies are used in many areas of research, including cell growth, tumour suppression, hypoxia and signal transduction. A tyrosine kinase receptor fundamental to cell growth and replication, EGFR has been proven to be an oncogene in a number of cancers, including lung, breast, anal and epithelial cancers. EGFR mutations can lead to overexpression or continuous activation of the protein, causing uncontrolled cell proliferation and tumour formation.
Many cancer studies have focussed on the development of EGFR inhibitors, which work directly against the protein. Various quantitative antibody assay techniques have been developed which identify EGFR inhibitors by detection of phosphorylation. These inhibitors form two groups. The first are small-molecule inhibitors like Gefitinib, erlotinib and lapatinib. These work by blocking tyrosine kinase activity of the receptor at its cytoplasmic domain, preventing promotion of EGFR to its active state and thus preventing binding and activation of downstream signalling proteins.
The second group are the monoclonal antibody inhibitors, which work by blocking the ligand binding domain on the extracellular side. Activation of tyrosine kinase is dependent upon successful binding of the EGF and TGF-alpha ligands. Antibody inhibitors may be further broken down into IgG1 antibodies, such as Cetuximab, and IgG2 antibodies, such as panitumumab. Each has quite different cytotoxic effects. Several other antibody-dependent inhibitors are in clinical development.
EGFR inhibitors of either type have been of limited success owing to intrinsic and acquired cellular resistance. Studies in lower eukaryotes have suggested that drug resistance could be due to protein networks closely associated with EGFR.
A recent study, conducted by Weiner et al, took this further by examining resistance in cancer cells. Small interfering RNA (siRNA) screening was used to identify proteins demonstrating resistance to both types of EGFR inhibitor drugs, and nonspecific cytotoxic agents. It was found that drugs targeting proteins within the EGFR core network, such as Aurora kinase A, protein kinase C and STAT3 interacted with EGFR inhibitors to reduce tumour cell size and viability. This suggests that future antibody studies into inhibitor therapies should focus, not only on EGFR itself, but on these associated proteins.
We at Novus Biologicals are one of the leading antibody suppliers for cancer research, with a large antibody database covering every aspect of EGFR activity.