title: Understanding the mechanisms of action of antiangiogenic agents in metastatic colorectal cancer: a clinician's perspective.
abstract: Multiple clinical trials using bevacizumab, ziv-aflibercept, and regorafenib have recently demonstrated efficacy for patients with metastatic colorectal cancer. While the net clinical benefit of each of these therapies in the second-line and refractory disease setting appears to be similar, important distinctions exist between the agents at the pharmacodynamic, tumor microenvironment, and clinical levels. The purpose of this review is to survey the preclinical evidence regarding the mechanisms of action of these novel antiangiogenic agents and provide an overview of their respective clinical activity, while highlighting distinctions between therapies. Fundamental understanding of these distinctions may aid in clinical decisions and choice of antiangiogenic therapies.
authors.affiliation: Duke Cancer Institute, DUMC 2823, Durham, NC 27710, USA. Electronic address: jeffrey.clarke@duke.edu.
authors.forename: J M
authors.initials: JM
authors.lastname: Clarke
authors.affiliation: Duke Cancer Institute, DUMC 2823, Durham, NC 27710, USA. Electronic address: herbert.hurwitz@duke.edu.
authors.forename: H I
authors.initials: HI
authors.lastname: Hurwitz
authors.affiliation: Duke Cancer Institute, DUMC 2823, Durham, NC 27710, USA; Oncology, GlaxoSmithKline Research and Development, Research Triangle Park, USA. Electronic address: Fatima.x.rangwala@gsk.com.
authors.forename: F
authors.initials: F
authors.lastname: Rangwala
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000068258:Bevacizumab; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D010671:Phenylurea Compounds / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D010671:Phenylurea Compounds; D011725:Pyridines; D011993:Recombinant Fusion Proteins; C533178:aflibercept; C559147:regorafenib; D000068258:Bevacizumab; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Angiogenesis; Antiangiogenic; Bevacizumab; Metastatic colorectal cancer; Ramucirumab; Regorafenib; Ziv-aflibercept