Cell signalling: growth factors and tyrosine kinase receptors

Clin Transl Oncol. 2006 Feb;8(2):77-82. doi: 10.1007/s12094-006-0162-1.


The mitogenic signaling in mammalian cells is carried out mainly by growth factors that interact with receptors localized at the plasma membrane. Most of these receptors have a tyrosine kinase activity domain that is localized at the cytoplasmic region of the molecule. The interaction of the growth factors with the receptors, besides inducing the kinase activity of the receptor, activate signaling pathways the alter gene expression patterns and induce mitogenesis, or if deregulated are related to cancer. Among these receptors ERBB, VEGF, PDGF and IGF are attractive targets for directed therapies. ERBB receptors are frequently involved in the production of many types of cancers. Both, the over-expression of the growth factor and the receptor, besides mutations at the cytoplasmic tyrosine kinase domain contribute to constitutive signaling in human cancer. VEGF has a pivotal role in maintaining the tumor growth by facilitating growth of new blood vessels. Therefore, inhibition of tumor growth targeting of the tumor vasculature, by interfering with the activity of VEGFr is now a real alternative in combinatorial therapies. PDGF is a growth factor involved in growth of connective tissue and wound healing. Activating mutations of PDGFr have been found in gastrointestinal tumors and the autocrine signaling maintained by this receptor have been described in many tumors. Imatinib, and inhibitor of the tyrosine kinase activity of Bcr-Abl targets also the kinase of the PDGFr. Finally IGF-I an II have an important antiapoptotic and pro-mitogenic role in most tumors. Different inhibitors are now under clinical studies for the use in combination of chemotherapeutic drugs in the treatment of different tumors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • ErbB Receptors / physiology
  • Genes, erbB
  • Genes, erbB-1
  • Genes, erbB-2
  • Growth Substances / physiology*
  • Humans
  • Ligands
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / physiology
  • Neoplasms / drug therapy
  • Neoplasms / physiopathology
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / physiopathology
  • Platelet-Derived Growth Factor / antagonists & inhibitors
  • Platelet-Derived Growth Factor / physiology
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / physiology
  • Receptor, ErbB-3 / antagonists & inhibitors
  • Receptor, ErbB-3 / physiology
  • Receptor, ErbB-4
  • Receptors, Somatomedin / antagonists & inhibitors
  • Receptors, Somatomedin / physiology
  • Signal Transduction* / physiology
  • Somatomedins / antagonists & inhibitors
  • Somatomedins / physiology
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / physiology


  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Growth Substances
  • Ligands
  • Neoplasm Proteins
  • Platelet-Derived Growth Factor
  • Protein Kinase Inhibitors
  • Receptors, Somatomedin
  • Somatomedins
  • Vascular Endothelial Growth Factor A
  • ERBB4 protein, human
  • ErbB Receptors
  • Receptor Protein-Tyrosine Kinases
  • Receptor, ErbB-2
  • Receptor, ErbB-3
  • Receptor, ErbB-4