Fig. 7

Targeting the EGFR signaling pathway. Epidermal growth factor receptor (EGFR/HER1) is a transmembrane protein receptor of the ErbB family, which also includes HER2/ErbB-2. EGFR pathway is frequently activated in colorectal cancer, through downstream RAS/MAPK and PI3K/AKT signaling pathways, leading to cell growth and proliferation. Anti-EGFR antibodies (such as cetuximab and panitumumab) bind to the extracellular domain of the EGFR preventing its activation. However, activating mutations of downstream modulators such as RAS, BRAF, PI3K, PTEN, or amplification/mutation of other ErbB receptors such as HER2 may confer resistance to anti-EGFR therapy