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Dasatinib inhibits the growth of prostate cancer in bone and provides additional protection from osteolysis
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 t...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720213/ https://www.ncbi.nlm.nih.gov/pubmed/19603032 http://dx.doi.org/10.1038/sj.bjc.6605178 |
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author | Koreckij, T Nguyen, H Brown, L G Yu, E Y Vessella, R L Corey, E |
author_facet | Koreckij, T Nguyen, H Brown, L G Yu, E Y Vessella, R L Corey, E |
author_sort | Koreckij, T |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2720213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-27202132009-09-21 Dasatinib inhibits the growth of prostate cancer in bone and provides additional protection from osteolysis Koreckij, T Nguyen, H Brown, L G Yu, E Y Vessella, R L Corey, E Br J Cancer Translational Therapeutics 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. Nature Publishing Group 2009-07-21 2009-07-14 /pmc/articles/PMC2720213/ /pubmed/19603032 http://dx.doi.org/10.1038/sj.bjc.6605178 Text en Copyright © 2009 Cancer Research UK https://creativecommons.org/licenses/by-nc-sa/3.0/This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/. |
spellingShingle | Translational Therapeutics Koreckij, T Nguyen, H Brown, L G Yu, E Y Vessella, R L Corey, E Dasatinib inhibits the growth of prostate cancer in bone and provides additional protection from osteolysis |
title | Dasatinib inhibits the growth of prostate cancer in bone and provides additional protection from osteolysis |
title_full | Dasatinib inhibits the growth of prostate cancer in bone and provides additional protection from osteolysis |
title_fullStr | Dasatinib inhibits the growth of prostate cancer in bone and provides additional protection from osteolysis |
title_full_unstemmed | Dasatinib inhibits the growth of prostate cancer in bone and provides additional protection from osteolysis |
title_short | Dasatinib inhibits the growth of prostate cancer in bone and provides additional protection from osteolysis |
title_sort | dasatinib inhibits the growth of prostate cancer in bone and provides additional protection from osteolysis |
topic | Translational Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720213/ https://www.ncbi.nlm.nih.gov/pubmed/19603032 http://dx.doi.org/10.1038/sj.bjc.6605178 |
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