Recent advances in small molecule inhibitors of VEGFR and EGFR signaling pathways

Curr Top Med Chem. 2011;11(12):1571-90. doi: 10.2174/156802611795860924.


Aberrant angiogenesis has been observed in many solid tumors. The formation and metastases of tumors such as non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) are very complex, often regulated by proangiogenic factors such as the vascular endothelial growth factor (VEGF) and other tyrosine kinases. The VEGFR, EGFR and mTOR pathways have played critical roles in controlling cell proliferation and angiogenesis. This paper reviews the mechanism and binding modes of recently approved tyrosine kinase inhibitors (TKIs), such as gefitinib, erlotinib, nilotinib, dasatinib, sunitinib, sorafenib, pazopanib, lapatinib, afinitor, and temsirolimus. We also cover the progresses of the recent development of tyrosine kinase inhibitors that are currently in the clinical trials at the phases I, II, and III, targeting the VEGFR, EGFR and/or mTOR pathways. Combination therapy intended to overcome drug resistance is also discussed. Recent TKI design based on the activation loop and the "DFG" conformation, is also discussed.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • ErbB Receptors / antagonists & inhibitors*
  • Humans
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
  • Signal Transduction / drug effects*


  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • ErbB Receptors
  • Receptors, Vascular Endothelial Growth Factor