The presence of BRAF mutations does not seem to fulfill this predictive

value. Studies to elucidate further the role of positive predictive markers are ongoing. Additionally, we need to deepen our understanding of the mechanisms that drive resistance to EGFR inhibitors to further refine selection and improve outcome. Agents that are thought to reverse resistance to EGFR inhibitors such as those targeting PI3K, c-MET, Her-3 or IGF-1R are currently under study. EGFR inhibitors Inhibitors,research,lifescience,medical have exhibited single agent activity, and seem to synergize very well with standard chemotherapy except for cetuximab and FOLFOX. Preliminary data suggests that EGFR inhibitors have similar effectiveness to VEGF inhibitors when combined with standard chemotherapy, with the definitive results from large randomized studies (FIRE-3, CALGB 80405) eagerly anticipated. Evidence suggests that strategies to combine EGFR and VEGF inhibitors in the first Inhibitors,research,lifescience,medical line setting can be detrimental to outcome. Skin toxicity remains the main limiting factor for the utilization of EGFR inhibitors, but strategies including the use of agents such as minocycline or doxycycline added to topical care seem to limit

the severity Inhibitors,research,lifescience,medical of the rash. Acknowledgements Disclosure: The authors declare no conflict of interest.
Colorectal cancer is a major cause of morbidity and mortality throughout the world. It is the third most common cancer diagnosis worldwide and affects men and women equally (1). In the United States, colorectal cancer accounted Inhibitors,research,lifescience,medical for 9% of all cancer mortality in 2012 (2). The survival of patients with metastatic colorectal cancer (mCRC) has markedly improved since the 1990s when 5-fluorouracil (5FU) based chemotherapy achieved an overall survival (OS)

of 12 months. The addition of oxaliplatin and Irinotecan increased the OS to approximately 18 months (3-6). The survival was further augmented with anti-angiogenic agents and bevacizumab, in combination with chemotherapy, was the first of the drug class to receive regulatory approval for use in mCRC therapy (7,8). Recently, 2 other anti-angiogenic drugs, aflibercept Inhibitors,research,lifescience,medical and regorafenib, were found to improve the survival of mCRC patients in randomized trials which further reiterates the importance of targeting angiogenesis in CRC therapy (9,10). This article will review the development of aflibercept and regorafenib and their AV-951 current role in the treatment of colorectal cancer (Table 1). Table 1 Compare bevacizumab, afibercept and regorafenib Tumor angiogenesis and VEGF signaling pathway Angiogenesis refers to a multi-step process leading to the formation of new blood vessels to supply nutrients and sellckchem oxygen to the tissues (11). The process begins with vasodilatation, increased vessel permeability, stromal degradation and endothelial cell proliferation and migration, resulting in the formation of a new or extended capillary (12).