Temsirolimus combined with cisplatin or bevacizumab is active in osteosarcoma models

Emmy D.G. Fleuren, Yvonne M.H. Versleijen-Jonkers, Melissa H.S. Roeffen, Gerben M. Franssen, Uta E. Flucke, Peter J. Houghton, Wim J.G. Oyen, Otto C. Boerman, Winette T.A. Van Der Graaf

Resultado de la investigación: Articlerevisión exhaustiva

22 Citas (Scopus)


Mammalian target of rapamycin (mTOR) is a new promising oncological target. However, most clinical studies reported only modest antitumor activity during mTOR-targeted monotherapies, including studies in osteosarcomas, emphasizing a need for improvement. We hypothesized that the combination with rationally selected other therapeutic agents may improve response. In this study, we examined the efficacy of the mTOR inhibitor temsirolimus combined with cisplatin or bevacizumab on the growth of human osteosarcoma xenografts (OS-33 and OS-1) in vivo, incorporating functional imaging techniques and microscopic analyses to unravel mechanisms of response. In both OS-33 and OS-1 models, the activity of temsirolimus was significantly enhanced by the addition of cisplatin (TC) or bevacizumab (TB). Extensive immunohistochemical analysis demonstrated apparent effects on tumor architecture, vasculature, apoptosis and the mTOR-pathway with combined treatments. 3′ -Deoxy- 3′ -18 F-fluorothymidine (18 F-FLT) positron emission tomography (PET) scans showed a remarkable decrease in 18F-FLT signal in TC- and TB-treated OS-1 tumors, which was already noticeable after 1 week of treatment. No baseline uptake was observed in the OS-33 model. Both immunohistochemistry and 18F-FLT-PET demonstrated that responses as determined by caliper measurements underestimated the actual tumor response. Although 18 F-FLT-PET could be used for accurate and early response monitoring for temsirolimus-based therapies in the OS-1 model, we could not evaluate OS-33 tumors with this molecular imaging technique. Further research on the value of the use of 18F-FLT-PET in this setting in osteosarcomas is warranted. Overall, these findings urge the further exploration of TC and TB treatment for osteosarcoma (and other cancer) patients.

Idioma originalEnglish (US)
Páginas (desde-hasta)2770-2782
Número de páginas13
PublicaciónInternational Journal of Cancer
EstadoPublished - dic. 15 2014
Publicado de forma externa

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Profundice en los temas de investigación de 'Temsirolimus combined with cisplatin or bevacizumab is active in osteosarcoma models'. En conjunto forman una huella única.

Citar esto