The inherited or acquired deregulation of
protein kinase activity has been implicated in the pathogenesis of many human diseases, including
cancer. Therefore, the inhibition of
kinases has been proposed to be a promising strategy in the context of anti-
cancer treatment. Many other
kinases have been selected as
drug discovery targets based on the prevalence of mutations, over-expression and unscheduled activation in human
cancer. Of the various
protein kinases chosen,
Src family kinases are amongst the most extensively studied
kinase oncogenes in academia and industry. This review focuses on our current understanding of the deregulation and role of
Src family kinases in human
cancer and
leukemia. Recent data implicate the action of c-Src in
cancer metastasis, mediated by up-regulation of various
protease systems (
calpain, uPA) as well as disruption of
E-cadherin signalling. Moreover, novel roles of various Src family members in the development of human
leukemia have been found. New insights into downstream signalling mechanisms, including the activation of STAT3, PDK1 and Akt, further corroborate the importance of
Src family kinases in
tumorigenesis and chemoresistance. Despite our rather clear understanding of
Src family kinases as pro-oncogenes no
Src family kinase inhibitor has entered a clinical trial so far. This review will discuss prerequisites to be fulfilled for clinically targeting c-Src and its homologues using small molecule drugs.