title: Targeting Angiogenesis in Colorectal Cancer: Tyrosine Kinase Inhibitors.
abstract: Colorectal cancer is commonly diagnosed throughout the world, and treatment options have greatly expanded over the last 2 decades. Targeting angiogenesis has been a major focus of study in a variety of malignancy types. Targeting angiogenesis has been achieved by several mechanisms in colorectal cancer, including use of antiangiogenic small molecule tyrosine kinase inhibitors (TKIs). There have been many attempts and failures to prove efficacy of TKIs in the treatment of colorectal cancer including sorafenib, sunitinib, vatalanib, and tivozanib. Regorafenib was the first TKI to demonstrate efficacy and is an orally active inhibitor of angiogenic (including the vascular endothelial growth factor receptors 1, 2, and 3), stromal, and oncogenic receptor tyrosine kinases. There are ongoing investigations of both regorafenib and ninetanib; however, there remains a critical need to better understand novel combinations with TKIs that could prove more efficacious than available options.
authors.affiliation: From the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
authors.forename: Sheetal Mehta
authors.initials: SM
authors.lastname: Kircher
authors.forename: Halla S
authors.initials: HS
authors.lastname: Nimeiri
authors.forename: Al B
authors.initials: AB
authors.lastname: Benson
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D055808:Drug Discovery; D006801:Humans; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D010671:Phenylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D042442:Vascular Endothelial Growth Factors; C559147:regorafenib