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.
Pohl
Alexandra
A
Division of Medical Oncology, Sharon A. Carpenter Laboratory, USC/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, California 90033, USA.
Zhang
Wu
W
Ning
Yan
Y
Manegold
Philipp C
PC
Lurje
Georg
G
Lenz
Heinz-Josef
HJ
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D009362:Neoplasm Metastasis; D018579:Patient Selection; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D066246:ErbB Receptors