Editorial [Hot Topic:Non-Receptor Tyrosine Kinases as Molecular Targets for Patient Tailored Cancer Therapy (Guest Editors: F.M. Uckun, A. Vassilev and H. Tibbles)]

Protein tyrosine kinases (PTKs) play important roles in biochemical signaling events related to cellular activation, differentiation, proliferation, and survival. Because of their contribution to chemotherapy resistance as well as growth of human cancers, several PTKs have emerged as new molecular targets in cancer therapy. The reported clinical successes with the anti- HER2 monoclonal antibody Herceptin in breast cancer, anti-EGFRI antibody Erbitux in colon cancer, and small molecule kinase inhibitor Gleevec in BCR-ABL positive leukemias have resulted in a paradigm-shift in treatment of cancer and sparked interest in tyrosine kinase inhibitors as a new class of promising drug candidates. In this issue, we explore the clinical potential of small molecule inhibitors targeting the JAK, SRC, TEC and FAK family of PTK. Many of these drug candidates in the PTK inhibitor pipeline have entered into clinical testing, while others are at advanced preclinical stages. Our issue begins with an overview by Gunby et al. entitled “Oncogenic fusion tyrosine kinases as molecular targets for anti-cancer therapy”. In two of the review articles, the potential of rationally designed selective tyrosine kinase inhibitors targeting JAK3 and BTK are discussed by Uckun, Vassilev, and Tibbles. In the article entitled “Non-Receptor Tyrosine Kinase Inhibitors in Lung Cancer”, Hahn and Salgia discuss the development of tyrosine kinase inhibitors for lung cancer. Godeny and Sayeski review the role of Janus Kinase 2 (Jak2) in both classical cellular signaling and neoplastic growth in “Jak2 Tyrosine Kinase and Cancer: How Good Cells Get HiJAKed”. In their article entitled “Src Family of Non-Receptor Tyrosine Kinases as Molecular Targets for Cancer Therapy”, Johnson and Gallick discuss the potential of SRC kinase inhibitors. Schenone, Manetti and Botta continue the discussion of SRC kinase inhibitors in their article “Synthetic Src-kinase domain inhibitors and their structural requirements”. Finally, in the review entitled “Role of Focal Adhesion Kinase in Human Cancer: A Potential Target for Drug Discovery”, Han and McGonigal discuss FAK kinase inhibitors. We are hopeful that these review articles will serve as a useful reference and guide for readers who are interested in learning more about the role of PTK in cancer biology and the clinical potential of PTK inhibitors.