Gholami, S, Chen, C-H, Gao, S, Lou, E, Fujisawa, S, Carson, J, Nnoli, JE, Chou, T-C, Bromberg, J, Fong, Y (July 2014) Role of MAPK in oncolytic herpes viral therapy in triple-negative breast cancer. Cancer Gene Therapy, 21 (7). pp. 283-289. ISSN 0929-1903
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.
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders > cancer > cancer types > breast cancer organism description > virus > herpes simplex virus |
| CSHL Authors: | |
| Communities: | CSHL labs > Gholami Lab |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | July 2014 |
| Date Deposited: | 05 Oct 2023 18:54 |
| Last Modified: | 05 Oct 2023 18:54 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/41145 |
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