The role of Src in prostate cancer.
The Src family kinases (SFKs) are the largest family of nonreceptor protein tyrosine kinases and are responsible for signal transduction during many cellular activities, including differentiation, adhesion, and migration. Aberrant Src/SFK activity has been widely implicated in cancer development. Several lines of evidence indicate a role for SFKs in the development of prostate cancer, e.g. SFK overexpression in prostate cancer cell lines and tissues and reduced cancer cell proliferation, invasion, and migration following Src inhibition. In particular, Src may be involved in androgen-independent growth during advanced stages of disease. Src signaling is also a key pathway during normal and dysregulated bone functioning, and bone metastases are responsible for substantial morbidity in advanced prostate cancer. Src/SFK inhibition therefore represents a potentially useful therapeutic strategy for patients with various stages of prostate cancer. To date, four Src inhibitors have reached clinical trials. Of these, the broadest range of in vitro prostate cancer data are available for dasatinib, which inhibits several SFKs as well as other tyrosine kinases. Src inhibitors may be specifically evaluated in prostate cancer clinical trials in the near future.
Fizazi
K
K
Department of Medicine, Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94800 Villejuif, France. fizazi@igr.fr
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D017322:Clinical Trials, Phase II as Topic; D000069439:Dasatinib; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology*; D009367:Neoplasm Staging; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000187:drug effects; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D019061:src-Family Kinases; D000069439:Dasatinib