Mechanisms of resistance to anti-epidermal growth factor receptor inhibitors in metastatic colorectal cancer

Figure 2 Mechanisms of resistance to anti-epidermal growth factor receptor monoclonal antibodies in metastatic colorectal cancer. A: Activating mutations of EGFR effectors, such as RAS, BRAF and PI3KCA, or PTEN loss of function, cause persistent activation of downstream signaling regardless of EGFR inhibition; B: Mutations in extracellular domain of EGFR inhibit cetuximab binding, but not panitumumab, mediating acquired resistance. Mutations in kinase domain of EGFR led pathways activation in the context of acquired resistance; C: Amplification/activation of alternative receptors such as HER2 or MET, can bypass the EGFR blockade and mediate pathways activation. EGFR: Epidermal growth factor receptor.