title: Novel approaches to the development of tyrosine kinase inhibitors and their role in the fight against cancer.
abstract: BACKGROUND
  Protein tyrosine kinase inhibitors are currently one of the most important classes of cancer drugs and one of the most impressive approaches of targeted cancer therapy. Aberrant activation of tyrosine kinase pathways is among the most dysregulated molecular pathways in human cancers; therefore, a large number of tyrosine kinases may serve as valuable molecular targets. To date, several inhibitors of tyrosine kinases have been approved and there are hundreds more compounds that are in various stages of development. Because of the deregulation in human malignancies, the ABL1, SRC, the epidermal growth factor receptor and the vascular endothelial growth factor receptor kinases are among the protein kinases that are considered as prime molecular targets for selective inhibition.
  
  
  METHODS
  This review focuses on most important small-molecule inhibitors that serve as a model for future development. They also provide a broad overview of some of the new approaches and challenges in the field.
  
  
  CONCLUSIONS
  With the exception of a few malignancies seemingly driven by a limited number of genetic lesions, current targeted therapeutic approaches have shown only limited efficacy in advanced cancers. Consequently, more sophisticated strategies, such as identification of pathogenic 'driver' mutations and optimization of personalized therapies are needed.
authors.affiliation: Kuwait Cancer Control Center, Department of Hematology, Laboratory of Cancer Genetics , PO Box 42262, 70653 , Kuwait +00965 24821363 ; +00965 24810007 ; annaadria@yahoo.com.
authors.forename: Adriana
authors.initials: A
authors.lastname: Zámečníkova
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases