SRC family kinases as potential therapeutic targets for malignancies and immunological disorders

Curr Med Chem. 2008;15(12):1154-65. doi: 10.2174/092986708784310404.

Abstract

The Src family consists of eight non-receptor protein tyrosine kinases characterised by a common structure. Based on their amino acid sequence, Src family kinases are grouped into two subfamilies, which are also characterised by different tissue specificity. Src kinases are involved in signal transduction pathways triggered by a wide variety of surface receptors, including receptor tyrosine kinases, integrins, G-protein-coupled receptors and antigen receptors. Several pieces of evidence implicate Src family kinases in cancer development, as a consequence of changes in protein expression and/or kinase activity, and have prompted the design of potent specific inhibitors, the most common of which are adenine mimetics, as tools of relevant clinical interest for the treatment of both solid tumours and leukaemias. In addition, the finding that some Src kinases expressed in haematopoietic cells play pivotal roles in lymphocyte maturation and activation has fostered the development of safe and effective inhibitors selective for specific Src family members, which are currently being tested in clinical trials as immunosuppressants for the treatment of immunological disorders. Here we shall review the recent literature on the involvement of Src family kinases in human neoplasias and immunological disorders and the goals reached in the search for selective pharmacological inhibitors.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Catalysis
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Immune System Diseases / drug therapy*
  • Immune System Diseases / enzymology
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / antagonists & inhibitors
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Receptors, Cell Surface / drug effects
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • src-Family Kinases / antagonists & inhibitors
  • src-Family Kinases / chemistry
  • src-Family Kinases / drug effects*

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Receptors, Cell Surface
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • src-Family Kinases