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Article

Pre-activation of the p53 pathway through Nutlin-3a sensitises sarcomas to drozitumab therapy

  • Authors:
    • Kathleen I. Pishas
    • Susan J. Neuhaus
    • Mark T. Clayer
    • Alaknanda Adwal
    • Michael P. Brown
    • Andreas Evdokiou
    • David F. Callen
    • Paul M. Neilsen
  • View Affiliations / Copyright

    Affiliations: Centre for Personalised Cancer Medicine, The University of Adelaide, Adelaide, South Australia, Australia, Department of Orthopaedics and Trauma, Royal Adelaide Hospital, Adelaide, South Australia, Australia, Sarcoma Research Group, Discipline of Medicine, The University of Adelaide, Adelaide, South Australia, Australia
  • Pages: 471-477
    |
    Published online on: May 13, 2013
       https://doi.org/10.3892/or.2013.2454
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Abstract

The present study evaluated the efficacy of drozitumab, a human monoclonal agonistic antibody directed against death receptor 5 (DR5), as a new therapeutic avenue for the targeted treatment of bone and soft-tissue sarcomas. The antitumour activity of drozitumab as a monotherapy or in combination with Nutlin-3a was evaluated in a panel of sarcoma cell lines in vitro and human sarcoma patient samples ex vivo. Knockdown experiments were used to investigate the central role of p53 as a regulator of drozitumab cytotoxicity. Pre-activation of the p53 pathway through Nutlin-3a upregulated DR5, subsequently sensitising sarcoma cell lines and human sarcoma specimens to the pro-apoptotic effects of drozitumab. Silencing of p53 strongly decreased DR5 mRNA expression resulting in abrogation of drozitumab-induced apoptosis. Our study provides the first pre-clinical evaluation of combination therapy using p53-activating agents with drozitumab to further sensitise sarcomas to the cytotoxic effects of DR5 antibody therapy.
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Copy and paste a formatted citation
Spandidos Publications style
Pishas KI, Neuhaus SJ, Clayer MT, Adwal A, Brown MP, Evdokiou A, Callen DF and Neilsen PM: Pre-activation of the p53 pathway through Nutlin-3a sensitises sarcomas to drozitumab therapy. Oncol Rep 30: 471-477, 2013.
APA
Pishas, K.I., Neuhaus, S.J., Clayer, M.T., Adwal, A., Brown, M.P., Evdokiou, A. ... Neilsen, P.M. (2013). Pre-activation of the p53 pathway through Nutlin-3a sensitises sarcomas to drozitumab therapy. Oncology Reports, 30, 471-477. https://doi.org/10.3892/or.2013.2454
MLA
Pishas, K. I., Neuhaus, S. J., Clayer, M. T., Adwal, A., Brown, M. P., Evdokiou, A., Callen, D. F., Neilsen, P. M."Pre-activation of the p53 pathway through Nutlin-3a sensitises sarcomas to drozitumab therapy". Oncology Reports 30.1 (2013): 471-477.
Chicago
Pishas, K. I., Neuhaus, S. J., Clayer, M. T., Adwal, A., Brown, M. P., Evdokiou, A., Callen, D. F., Neilsen, P. M."Pre-activation of the p53 pathway through Nutlin-3a sensitises sarcomas to drozitumab therapy". Oncology Reports 30, no. 1 (2013): 471-477. https://doi.org/10.3892/or.2013.2454
Copy and paste a formatted citation
x
Spandidos Publications style
Pishas KI, Neuhaus SJ, Clayer MT, Adwal A, Brown MP, Evdokiou A, Callen DF and Neilsen PM: Pre-activation of the p53 pathway through Nutlin-3a sensitises sarcomas to drozitumab therapy. Oncol Rep 30: 471-477, 2013.
APA
Pishas, K.I., Neuhaus, S.J., Clayer, M.T., Adwal, A., Brown, M.P., Evdokiou, A. ... Neilsen, P.M. (2013). Pre-activation of the p53 pathway through Nutlin-3a sensitises sarcomas to drozitumab therapy. Oncology Reports, 30, 471-477. https://doi.org/10.3892/or.2013.2454
MLA
Pishas, K. I., Neuhaus, S. J., Clayer, M. T., Adwal, A., Brown, M. P., Evdokiou, A., Callen, D. F., Neilsen, P. M."Pre-activation of the p53 pathway through Nutlin-3a sensitises sarcomas to drozitumab therapy". Oncology Reports 30.1 (2013): 471-477.
Chicago
Pishas, K. I., Neuhaus, S. J., Clayer, M. T., Adwal, A., Brown, M. P., Evdokiou, A., Callen, D. F., Neilsen, P. M."Pre-activation of the p53 pathway through Nutlin-3a sensitises sarcomas to drozitumab therapy". Oncology Reports 30, no. 1 (2013): 471-477. https://doi.org/10.3892/or.2013.2454
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