Preclinical evaluation of Sunitinib as a single agent in the prophylactic setting in a mouse model of bone metastases

BMC Cancer

Christian Schem³  Dirk Bauerschlag¹  Sascha Bender³  Ann-Christin Lorenzen³  Daniel Loermann³  Sigrid Hamann³  Frank Rösel³  Holger Kalthoff²  Claus C Glüer⁴  Walter Jonat³  Sanjay Tiwari⁴ 

[1] Department of Gynecology, University Hospital Aachen, Aachen, Germany

[2] Division of Molecular Oncology, Institute for Experimental Cancer Research, University Hospital Schleswig-Holstein , Campus Kiel, Germany

[3] Department of Gynecology, University Hospital Schleswig-Holstein, Campus Kiel, Germany

[4] Molecular Imaging North Competence Center, Department of Diagnostic Radiology, University Hospital Schleswig-Holstein, Campus Kiel, Germany

关键词: Imaging;    Breast cancer;    Bone metastases;    Sunitinib;   

Others  :  1079958
DOI  :  10.1186/1471-2407-13-32

 received in 2012-08-01, accepted in 2013-01-15,  发布年份 2013

【 摘 要 】

Background

A substantial number of breast cancer patients are identified as being at high risk of developing metastatic disease. With increasing number of targeted therapeutics entering clinical trials, chronic administration of these agents may be a feasible approach for the prevention of metastases within this subgroup of patients. In this preclinical study we examined whether Sunitinib, a multi-tyrosine kinase inhibitor which has anti-angiogenic and anti-resorptive activity, is effective in the prevention of bone metastases.

Method

Sunitinib was administered daily with the first dose commencing prior to tumor cell inoculation. Intracardiac injection was performed with MDA-MB23 bone-seeking cells, which were stably transfected with DsRed2. In vivo plain radiography and fluorescent imaging (Berthold NightOwl) was used in the analysis of bone metastases. Histomorphometry was used for the quantification of TRAP⁺ cells from bone sections and immunohistochemistry was performed using an antibody reactive to CD34 for quantification of microvessel density.

Results

Preventive dosing administration of Sunitinib does not inhibit colonization of tumor cells to bone or reduce the size of osteolytic lesions. There was a decrease in the number of TRAP⁺ cells with Sunitinib treatment but this did not reach significance. Sunitinib inhibited tumor growth as determined by imaging of fluorescent tumor area. Immunohistochemical analyses of microvessel density revealed a concomitant decrease in the number of tumor blood vessels.

Conclusions

The findings suggest that Sunitinib can be used as a therapeutic agent for the treatment of bone metastases but as a single agent it is not effective in terms of prevention. Therefore a combination approach with other cytostatic drugs should be pursued.

【 授权许可】

   
2013 Schem et al.; licensee BioMed Central Ltd.

【 图 表 】

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