Molecular testing for colorectal cancer: Clinical applications

Figure 1 Molecular cascades underlying colorectal cancer responsiveness and resistance to targeted therapy. Virtually all colorectal cancers (CRCs) are characterized by upregulation of mitogen-activated protein kinases (MAPK) signaling pathway. If MAPK cascade is activated by epidermal growth factor receptor (EGFR) receptor, the administration of anti-EGFR therapeutic antibodies results in the cessation of tumor growth. There are instances of EGFR-independent activation of MAPK pathway caused by mutations in the molecules located downstream to EGFR (KRAS, NRAS or BRAF) or by collateral signaling (e.g., HER2 overexpression); these CRCs are resistant to EGFR blockade, however they may be sensitive to appropriate targeted drugs. CRC: Colorectal cancer; EGFR: Epidermal growth factor receptor.