Br J Cancer. 2009 Jul 21;101(2):263-8.
Dasatinib inhibits the growth of prostate cancer in bone and provides additional protection from osteolysis.
Koreckij T, Nguyen H, Brown LG, Yu EY, Vessella RL, Corey E.
Department of Urology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA.
Dasatinib is a small molecule kinase inhibitor that has recently been
shown to inhibit Src family kinases (SFK) and also has activity against
CaP. Of importance to metastatic CaP, which frequently metastasises to
bone, SFK are also vital to the regulation of bone remodelling. We
sought to determine the ability of dasatinib to inhibit growth of CaP
METHODS: C4-2B CaP cells were injected into tibiae of SCID
mice and treated with dasatinib, alone or in combination with
docetaxel. Serum prostate-specific antigen levels, bone mineral
density, radiographs and histology were analysed. RESULTS: Treatment
with dasatinib alone significantly lowered sacrifice serum
prostate-specific antigen levels compared to control, 2.3+/-0.4 vs
9.2+/-2.1 (P=0.004). Combination therapy improved efficacy over
dasatinib alone (P=0.010). Dasatinib increased bone mineral density in
tumoured tibiae by 25% over control tumoured tibiae (P<0.001).
CONCLUSION: Dasatinib inhibits growth of C4-2B cells in bone with
improved efficacy when combined with docetaxel. Additionally, dasatinib
inhibits osteolysis associated with CaP. These data support further
study of dasatinib in clinical trials for men with CaP bone metastases.