Role of MAPK in oncolytic herpes viral therapy in triple-negative breast cancer

Sepideh Gholami, C. H. Chen, S. Gao, E. Lou, S. Fujisawa, J. Carson, J. E. Nnoli, T. C. Chou, J. Bromberg, Y. Fong

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Triple-negative breast cancers (TNBCs) have poor clinical outcomes owing to a lack of targeted therapies. Activation of the MEK/MAPK pathway in TNBC has been associated with resistance to conventional chemotherapy and biologic agents and has a significant role in poor clinical outcomes. NV1066, a replication-competent herpes virus, infected, replicated in and killed all TNBC cell lines (MDA-MB-231, HCC1806, HCC38, HCC1937, HCC1143) tested. Greater than 90% cell kill was achieved in more-sensitive lines (MDA-MB-231, HCC1806, HCC38) by day 6 at a multiplicity of infection (MOI) of 0.1. In less-sensitive lines (HCC1937, HCC1143), NV1066 still achieved >70% cell kill by day 7 (MOI 1.0). In vivo, mean volume of flank tumors 14 days after treatment with NV1066 was 57 versus 438 mm 3 in controls (P=0.002). NV1066 significantly downregulated p-MAPK activation by 48 h in all cell lines in vitro and in MDA-MB-231 xenografts in vivo. NV1066 demonstrated synergistic effects with a MEK inhibitor, PD98059 in vitro. We demonstrate that oncolytic viral therapy (NV1066) effectively treats TNBC with correlation to decreased MEK/MAPK signaling. These findings merit future studies investigating the potential role of NV1066 as a sensitizing agent for conventional chemotherapeutic and biologic agents by downregulating the MAPK signaling pathway.

Original languageEnglish (US)
Pages (from-to)283-289
Number of pages7
JournalCancer Gene Therapy
Volume21
Issue number7
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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  • Cite this

    Gholami, S., Chen, C. H., Gao, S., Lou, E., Fujisawa, S., Carson, J., Nnoli, J. E., Chou, T. C., Bromberg, J., & Fong, Y. (2014). Role of MAPK in oncolytic herpes viral therapy in triple-negative breast cancer. Cancer Gene Therapy, 21(7), 283-289. https://doi.org/10.1038/cgt.2014.28