Antiangiogenic tyrosine kinase inhibitors in metastatic colorectal cancer: Focusing on regorafenib

Abstract

The progress of metastatic colorectal cancer (mCRC) depends essentially on two signaling pathways: the first mediated by vascular endothelial growth factor (VEGF) and the second by epidermal growth factor receptor (EGFR). In colorectal cancer (CRC), the balance between pro-angiogenic and anti-angiogenic factors is disturbed in favor of a proangiogenic outcome (angiogenic switch) early in the neoplastic progression of adenomas, thus, resulting in neovascularization and eventually in malignant tumor progression. Furthermore, angiogenesis plays an important role in tumor growth and the formation of metastases. Several angiogenic growth factors have been identified to be highly expressed during the progression and metastatic spread of CRC, but VEGFA is the predominant angiogenic cytokine and the most consistently expressed factor during the metastatic process. Agents targeting VEGF/VEGFR signaling have shown efficacy in the treatment of mCRC and are currently approved in this setting. In this review, we summarize the role of antiangiogenic tyrosine kinase inhibitors (TKIs) in the treatment of mCRC, focusing on regorafenib.