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

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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

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Triple Negative Breast Neoplasms
Mitogen-Activated Protein Kinase Kinases
Biological Factors
Down-Regulation
Cell Line
Therapeutics
Infection
Tumor Burden
Heterografts
Viruses
Drug Therapy
In Vitro Techniques

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

Cite this

Gholami, S., Chen, C. H., Gao, S., Lou, E., Fujisawa, S., Carson, 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

Role of MAPK in oncolytic herpes viral therapy in triple-negative breast cancer. / Gholami, Sepideh; Chen, C. H.; Gao, S.; Lou, E.; Fujisawa, S.; Carson, J.; Nnoli, J. E.; Chou, T. C.; Bromberg, J.; Fong, Y.

In: Cancer Gene Therapy, Vol. 21, No. 7, 01.01.2014, p. 283-289.

Research output: Contribution to journalArticle

Gholami, S, Chen, CH, Gao, S, Lou, E, Fujisawa, S, Carson, J, Nnoli, JE, Chou, TC, Bromberg, J & Fong, Y 2014, 'Role of MAPK in oncolytic herpes viral therapy in triple-negative breast cancer', Cancer Gene Therapy, vol. 21, no. 7, pp. 283-289. https://doi.org/10.1038/cgt.2014.28
Gholami, Sepideh ; Chen, C. H. ; Gao, S. ; Lou, E. ; Fujisawa, S. ; Carson, J. ; Nnoli, J. E. ; Chou, T. C. ; Bromberg, J. ; Fong, Y. / Role of MAPK in oncolytic herpes viral therapy in triple-negative breast cancer. In: Cancer Gene Therapy. 2014 ; Vol. 21, No. 7. pp. 283-289.
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