Rationally designed treatment for metastatic colorectal cancer: Current drug development strategies

Core Tip

Core tip: Abrogation of the mitogen-activated protein kinase pathway downstream epidermal growth factor receptor (EGFR) has emerged as a new potential targetable pathway in the treatment of metastatic colorectal cancer. Similarly, a variety of agents blocking the PI3K/Akt/mTOR pathway are underway. At the same time, a combinatorial inhibition of angiogenesis is being attempted with dual blockade of vascular-endothelial growth factor and c-mesenchymal-epithelial transition factor. Indications that HER-2 overactivation can confer resistance to treatment to MoAb against EGFR has revealed yet another potential target whereas PARP inhibitors are being tested for their ability to cause synthetic lethality in cancer cells with established defects in MMR system.