Current status of small-molecule tyrosine kinase inhibitors targeting epidermal growth factor receptor in colorectal cancer.

摘要: Abstract The epidermal growth factor receptor (EGFR) is expressed in the majority of colorectal cancers (CRCs) and associated with poor clinical outcome. Ample evidence suggests that inhibition this pathway by monoclonal antibodies directed against EGFR leads to antitumor activity CRC. Small-molecule tyrosine kinase inhibitors (TKIs) provide distinct advantages over virtue lower production costs, ease oral administration, ability target multiple cellular survival pathways. Despite theoretical advantages, early-phase trials TKIs fail demonstrate single-agent However, unusually high response rates observed when gefitinib, an TKI, combined chemotherapy for patients metastatic CRC suggest a possible synergistic effect. This effect not seen non—small-cell lung cancer (NSCLC), which larger phase III have been conducted. differences between NSCLC respect expression mutation status do completely explain dichotomy, further investigation into pharmacogenomics under way. Significant effort toward newer strategies targeted at A new generation small-molecule emerging pathways, including ErbB2 vascular endothelial receptor, can be simultaneously EGFR. These agents are still trials, specific data forthcoming.