Recent Advances in the Signal Transduction Targeting of Colorectal Cancer: The Paradigm of Translational Medicine

Haralabos      Kalofonos; Petros   D.   Grivas

Abstract

The dynamic cross-talk between bench – based research and clinical practice is the fundamental characteristic of modern oncology. Colorectal cancer, the second most common cause of cancer – related death in the Western world, is the paradigm of the revolutionary use of targeted sophisticated therapies. The continuous unraveling of the molecular identity of signaling pathways that govern sub-cellular decisions reveals candidate targets. The epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) signaling pathways are considered major tumor-promoting cascades. Three monoclonal antibodies have been approved for the management of metastatic colorectal cancer. Cetuximab and panitumumab target the EGFR-signaling pathway, inhibiting the aberrant transduction of tumor – proliferating signals, as well as promoting tumor cell apoptosis. Bevacizumab is the first antibody inhibiting VEGF – driven formation of new blood vessels, a critical component of tumor metastasis. Randomized clinical trials in patients with colorectal cancer have shown significant clinical benefit and tolerable toxicity with the use of these antibodies. At the era of clinical bioinformatics, better selection of patient subpopulations with tumor-over-expressing specific clinical biomarkers could result in significant enhancement of signal transduction targeting success. This review discusses characteristics of cancer-associated signaling, describes the mechanism of action of the three monoclonal antibodies, focusing on their current role in the management of colorectal cancer.

Keywords: Colorectal cancer, signaling, monoclonal antibodies, cetuximab, panitumumab, bevacizumab