Novel epi-virotherapeutic treatment of pancreatic cancer combining the oral histone deacetylase inhibitor resminostat with oncolytic measles vaccine virus

  • Authors:
    • Tim Patrick Ellerhoff
    • Susanne Berchtold
    • Sascha Venturelli
    • Markus Burkard
    • Irina Smirnow
    • Tanja Wulff
    • Ulrich M. Lauer
  • View Affiliations

  • Published online on: August 31, 2016     https://doi.org/10.3892/ijo.2016.3675
  • Pages: 1931-1944
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Abstract

Oncolytic viruses (OV) constitute highly promising innovative biological anticancer agents. However, like every other antitumoral compound, OV are also faced with both primary and secondary mechanisms of resistance. To overcome those barriers and moreover amplify the therapeutic potential of OV, we evaluated a novel combined approach composed of the oral histone deacetylase inhibitor resminostat and an oncolytic measles vaccine virus (MeV) for a future epi‑virotherapy of pancreatic ductal adenocarcinoma. Cytotoxicity assays revealed that combined epi-virotherapeutic treatment of four well-characterized human pancreatic cancer cell lines resulted in a beneficial tumor cell killing as compared to either monotherapeutic approach. Notably, epi-virotherapeutic treatment of MIA PaCa-2 and partly also of PANC‑1 pancreatic cancer cells resulted in a tumor cell mass reduction being significantly more pronounced than it would be expected in case of an additive effect only, indicating a synergistic mode of action when combining resminostat with MeV. We further found that the epigenetic compound resminostat neither impaired MeV growth kinetics nor prevented the activation of the interferon signaling pathway which plays an important role in mediating primary and secondary resistances to OV. Moreover, we yielded information that the pharma­codynamic function of resminostat was presumably not altered in the course of pancreatic cancer cell infections with MeV. Taken together, these promising results favor the onset of epi-viro­thera­peutic clinical trials in patients suffering from advanced pancreatic ductal adenocarcinoma.
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November-2016
Volume 49 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Ellerhoff TP, Berchtold S, Venturelli S, Burkard M, Smirnow I, Wulff T and Lauer UM: Novel epi-virotherapeutic treatment of pancreatic cancer combining the oral histone deacetylase inhibitor resminostat with oncolytic measles vaccine virus. Int J Oncol 49: 1931-1944, 2016
APA
Ellerhoff, T.P., Berchtold, S., Venturelli, S., Burkard, M., Smirnow, I., Wulff, T., & Lauer, U.M. (2016). Novel epi-virotherapeutic treatment of pancreatic cancer combining the oral histone deacetylase inhibitor resminostat with oncolytic measles vaccine virus. International Journal of Oncology, 49, 1931-1944. https://doi.org/10.3892/ijo.2016.3675
MLA
Ellerhoff, T. P., Berchtold, S., Venturelli, S., Burkard, M., Smirnow, I., Wulff, T., Lauer, U. M."Novel epi-virotherapeutic treatment of pancreatic cancer combining the oral histone deacetylase inhibitor resminostat with oncolytic measles vaccine virus". International Journal of Oncology 49.5 (2016): 1931-1944.
Chicago
Ellerhoff, T. P., Berchtold, S., Venturelli, S., Burkard, M., Smirnow, I., Wulff, T., Lauer, U. M."Novel epi-virotherapeutic treatment of pancreatic cancer combining the oral histone deacetylase inhibitor resminostat with oncolytic measles vaccine virus". International Journal of Oncology 49, no. 5 (2016): 1931-1944. https://doi.org/10.3892/ijo.2016.3675