Herpes Tips

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

Breast tumors can be classified according to their gene-expression profiles into different molecular subtypes with distinct biological and clinical features. We have developed a novel recombinant HSV-1 virus (JS1/34.5−/47−) for purging of occult breast cancer cells from bone marrow of patients. METHODS: Human breast cancer MDA-MB-435 cells were cultured or implanted subcutaneously in BALB/c nude mice. In addition to that, the rash is some sort of allergic reaction to SOMETHING! 21% had T3- to T4-tumors, 55% had axillary lymph node involvement, and 65% received additional systemic hormonal and/or cytotoxic therapy. The parotids are located inside the cheeks, one below each ear. We have previously described an oncolytic herpes simplex virus (HSV), designated M002, which lacks both copies of the γ134.5 neurovirulence gene and carries a murine interleukin 12 (IL-12) expression cassette, and have validated its antitumor efficacy in a variety of preclinical models of primary brain tumors.

All patients were monitored for local and systemic adverse effects, and the nodules were excised 14 days after viral injection for histopathological studies. The reports indicate hereditary breast cancers are responsible for 4–10% of breast carcinomas [4,5,6]. G47Δ was highly cytotoxic for CD44+CD24-/low cells in vitro at both low MOIs (Table). Chronic disease in the Childhood Cancer Survivor Study cohort: a review of published findings. 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). These subtypes include basal like, ERBB2+, normal breast-like, luminal subtype A, and B (1). The Tzanck smear on her left anterior chest showed multinucleated giant cells with intranuclear inclusion bodies. Cancer cells aren’t as savvy, and T-Vec has its run of them. Increasingly, viral characteristics must be paired with the disease target (). 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. © 2014 Nature America, Inc.

AB – 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. Two weeks later, the number of wells containing mammospheres (diameter >40 μm) was recorded.