Dasatinib inhibits the growth of prostate cancer in bone and provides additional protection from osteolysis

Br J Cancer. 2009 Jul 21;101(2):263-8. doi: 10.1038/sj.bjc.6605178.


Background: 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 in bone.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Bone Density / drug effects
  • Bone Neoplasms / blood
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / secondary*
  • Cell Line, Tumor
  • Dasatinib
  • Docetaxel
  • Humans
  • Male
  • Mice
  • Mice, SCID
  • Osteolysis / blood
  • Osteolysis / drug therapy*
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrimidines / adverse effects
  • Pyrimidines / pharmacology*
  • Taxoids / administration & dosage
  • Thiazoles / adverse effects
  • Thiazoles / pharmacology*
  • Xenograft Model Antitumor Assays
  • src-Family Kinases / antagonists & inhibitors


  • Protein Kinase Inhibitors
  • Pyrimidines
  • Taxoids
  • Thiazoles
  • Docetaxel
  • src-Family Kinases
  • Prostate-Specific Antigen
  • Dasatinib