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2-Methoxyestradiol analogue ENMD-1198 reduces breast cancer induced osteolysis and tumor burden both in vitro and in vivo.
MedLine Citation:
PMID:  21422268     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
It has been estimated that 70% of advanced breast cancer patients will face the complication of bone metastases. Three processes are pivotal during bone metastatic growth of breast cancer namely, tumor cell proliferation, angiogenesis and osteolysis. During tumor-induced osteolysis, a number of cytokines and growth factors are released from the degraded bone matrix. These factors stimulate further tumor growth, tumor angiogenesis and tumor-induced osteolysis. New therapies should target all relevant processes to halt this powerful feedback loop. Here, we characterized the new 2-methoxyestradiol analogue ENMD-1198 and showed that ENMD-1198 is cytotoxic to tumor cells. Moreover, it showed both anti-angiogenic and vascular disruptive properties and was capable of protecting the bone against tumor-induced osteolysis. We confirmed the in vitro data with a series of in vivo experiments showing the beneficial effects of ENMD-1198 and ENMD-1198-based combination treatments of metastatic breast cancer in bone both on tumor progression and on survival with long term ENMD-1198 treatment. We confirmed the in vivo relevance of the ENMD-1198 protective effect on bone both with X-ray radiographs and micro-CT. In addition, we combined ENMD-1198 treatment with low dose "metronomic" cyclophosphamide and the bisphosphonate, risedronic acid, leading to a mild increase in treatment efficacy.
Authors:
Thomas Ja Snoeks; Isabel M Mol; Ivo Que; Eric L Kaijzel; Clemens W G M Lowik
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-21
Journal Detail:
Title:  Molecular cancer therapeutics     Volume:  -     ISSN:  1538-8514     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101132535     Medline TA:  Mol Cancer Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Endocrinology and Metabolic Diseases, Leiden University Medical Center.
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