Targeting metastatic colorectal cancer in 2008: a long way from 5-FU

Colorectal cancer is one of the leading causes of cancer-related death worldwide, with almost 20% of all patients presenting with metastatic disease at the time of their diagnosis. The treatment regimens and options of metastatic colorectal cancer have significantly changed in the last 10 years, leading to an improvement of response rates to about 50%, progression-free survival of about 10 months, and overall survival reaching over 2 years. Beside US Food and Drug Administration approval of the cytotoxic agents irinotecan (Camptosar), oxaliplatin (Eloxatin), and capecitabine (Xeloda), the increasing understanding of molecular pathways that comprise the cell cycle, apoptosis, angiogenesis, and invasion has provided novel targets in cancer therapy. The biologic agent bevacizumab (Avastin), an inhibitor against vascular endothelial growth factor, and cetuximab (Erbitux) and panitumumab (Vectibix), monoclonal antibodies to epidermal growth factor receptor, have demonstrated their efficacy in clinical trials. This article reviews the mechanisms of action and possible markers of resistance, and summarizes data on the clinical efficacy of targeting agents.