Vascular endothelial growth factor receptor tyrosine kinase inhibitors for the treatment of advanced non-small cell lung cancer

Expert Opin Pharmacother. 2020 Mar;21(4):491-506. doi: 10.1080/14656566.2020.1713092. Epub 2020 Jan 20.

Abstract

Introduction: Angiogenesis is the process by which the tumor develops its potential for growth and distant metastasis. The main proangiogenic switch is vascular endothelial growth factor (VEGF), which, along with its receptor VEGFR, is a target for biological drugs such as multi-targeted tyrosine kinase inhibitors used for many neoplasms, including non-small cell lung cancer (NSCLC).Areas covered: The fact that angiokinase inhibitors act on several signaling molecules simultaneously means that the use of alternative transmission pathways, which nullifies the effect of drugs directed against a single target, is avoided. Nevertheless, most of these drugs have failed to improve any outcome in NSCLC patients. The authors discuss these points and provide their expert perspectives.Expert opinion: Multikinase inhibitors are the fruit of research which regards cancer as a complex system of interacting processes. However, the lack of predictive biomarkers of response has limited the development of this class of drugs in NSCLC. Combination trials with chemotherapy, immunotherapy or other targeted drugs are ongoing, and while some have already confirmed the role of antiangiogenic small molecules in integrated regimes, others are still evaluating the efficacy of these drugs and raising questions about their cost and tolerability.

Keywords: Angiogenesis; NSCLC; TKIs; VEGF; VEGFR tyrosine kinase inhibitors; anlotinib; antiangiogenic therapy; molecular targeted drugs; nintedanib; second-line treatment.

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Protein Kinase Inhibitors / therapeutic use*
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors*

Substances

  • Angiogenesis Inhibitors
  • Protein Kinase Inhibitors
  • Vascular Endothelial Growth Factor A
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1