New approaches and targets in advanced colorectal cancer

The prognosis of cancer remains poor in spite of the advances obtained in recent years with new therapeutic agents, new approaches in surgical procedures and new diagnostic methods. An emerging understanding of the molecular pathways that characterise cell growth, cell cycle, apoptosis, angiogenesis and invasion has led to the identification of novel targets for cancer therapy. Numerous proteins have been implicated as having a crucial role in colorectal cancer (CRC). The targets can be grouped according to their cellular localisation such as membrane receptor targets (epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), insulinlike growth factor receptor (IGFR), platelet-derived growth factor receptor (PDGFR), tumour necrosis factor-related apoptosis-inducing ligand receptor (TRAIL-R), and c-Met), intracellular signalling targets (Ras/Raf/MAPK pathway, phosphatidylinositol3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), src kinase and p53/Hdm2) and other protein kinases that regulate cell division including aurora kinases and polo-like kinases (Fig. 1). Emerging data from the clinical development of new drugs directed to these targets is providing novel opportunities in the treatment of patients with CRC that will probably translate into efficacy benefits in the coming years.