New target agents in the treatment of colorectal cancer patients: the era after cetuximab and bevacizumab

Colorectal cancer (CRC) is the third most common cancer in the Western world. Approximately 60% of patients with CRC require systemic therapy for metastatic disease, either at diagnosis or at disease recurrence. Until recently, classic chemotherapeutic agents have been combined in the treatment of advanced CRC. Novel targeted agents, such as the anti-vascular endothelial growth factor monoclonal antibody bevacizumab or anti-human epidermal growth factor receptor-directed compounds (e.g., cetuximab), have demonstrated substantial efficacy in large clinical trials. Early evidence suggests potential synergism among these classes of compounds or with conventional chemotherapy. The relationships between growth factors, cell surface receptors and their second messengers in the development and progression of human malignancies are not new concepts. The use of therapeutic targeting of these molecular structures in colorectal cancer is enhancing the treatment of colorectal cancer. This review briefly overviews the clinical status of new drugs, after the antibodies cetuximab and bevacizumab, from various mechanistic groups, discussing their advancement in clinical development towards their use in CRC.