Understanding the mechanisms of action of antiangiogenic agents in metastatic colorectal cancer: a clinician's perspective

Cancer Treat Rev. 2014 Oct;40(9):1065-72. doi: 10.1016/j.ctrv.2014.07.001. Epub 2014 Jul 11.

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.

Keywords: Angiogenesis; Antiangiogenic; Bevacizumab; Metastatic colorectal cancer; Ramucirumab; Regorafenib; Ziv-aflibercept.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Bevacizumab
  • Clinical Trials, Phase III as Topic
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Drug Screening Assays, Antitumor
  • Humans
  • Phenylurea Compounds / therapeutic use
  • Pyridines / therapeutic use
  • Receptors, Vascular Endothelial Growth Factor / therapeutic use
  • Recombinant Fusion Proteins / therapeutic use
  • Tumor Microenvironment / drug effects

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Phenylurea Compounds
  • Pyridines
  • Recombinant Fusion Proteins
  • aflibercept
  • regorafenib
  • Bevacizumab
  • Receptors, Vascular Endothelial Growth Factor