Targeted biotherapy in metastatic colorectal carcinoma: Current practice

Targeted therapy has become an indispensable tool in the management of metastatic colorectal cancer (mCRC). The combination of monoclonal antibodies with conventional polychemotherapy has proven its efficacy as the median overall survival now exceeds 24 months: these novel molecules act by targeting circulating vascular endothelial growth factor (VEGF) and the receptor of epidermal growth factor (EGFR). At the present time, no factor has been identified to predict the efficacy of bevacizumab, an inhibitor of circulating VEGF. On the other hand, mutation of the KRAS oncogen has been proven to be a factor of non-response, or even of deleterious response to the use of EGFR, therefore limiting its use to patients whose tumors bear the wild type KRAS oncogen. Treatment toxicity for these molecules is moderate, specific, and is not cumulative with chemotherapy-related toxicity. On the other hand, combined targeted therapy (association of several targeted therapy drugs) has not been shown to be of any benefit. Other biotherapies continue to be developed, but there is not yet a consensus of how to best target the tumor nor which anti-tumoral molecules to use in the treatment of mCRC.