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NF-?B Signaling in Targeting Tumor Cells by Oncolytic Viruses-Therapeutic Perspectives.

ABSTRACT: In recent years, oncolytic virotherapy became a promising therapeutic approach, leading to the introduction of a novel generation of anticancer drugs. However, despite evoking an antitumor response, introducing an oncolytic virus (OV) to the patient is still inefficient to overcome both tumor protective mechanisms and the limitation of viral replication by the host. In cancer treatment, nuclear factor (NF)-?B has been extensively studied among important therapeutic targets. The pleiotropic nature of NF-?B transcription factor includes its involvement in immunity and tumorigenesis. Therefore, in many types of cancer, aberrant activation of NF-?B can be observed. At the same time, the activity of NF-?B can be modified by OVs, which trigger an immune response and modulate NF-?B signaling. Due to the limitation of a monotherapy exploiting OVs only, the antitumor effect can be enhanced by combining OV with NF-?B-modulating drugs. This review describes the influence of OVs on NF-?B activation in tumor cells showing NF-?B signaling as an important aspect, which should be taken into consideration when targeting tumor cells by OVs.

SUBMITTER: Struzik J

PROVIDER: S-EPMC6265863 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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NF-κB Signaling in Targeting Tumor Cells by Oncolytic Viruses-Therapeutic Perspectives.

Struzik Justyna J Szulc-Dąbrowska Lidia L

Cancers 20181108 11

In recent years, oncolytic virotherapy became a promising therapeutic approach, leading to the introduction of a novel generation of anticancer drugs. However, despite evoking an antitumor response, introducing an oncolytic virus (OV) to the patient is still inefficient to overcome both tumor protective mechanisms and the limitation of viral replication by the host. In cancer treatment, nuclear factor (NF)-κB has been extensively studied among important therapeutic targets. The pleiotropic natur ...[more]

PMID: 30413032

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Project description:BackgroundWith few exceptions, current chemotherapy and radiotherapy protocols only obtain a slightly prolonged survival with severe adverse effects in patients with advanced solid tumors. In particular, most solid malignancies not amenable to radical surgery still carry a dismal prognosis, which unfortunately is also the case for relapsing disease after surgery. Even though targeted therapies obtained good results, clinical experience showed that tumors eventually develop resistance. On the other hand, earlier attempts of cancer immunotherapy failed to show consistent efficacy. More recently, a deeper knowledge of immunosuppression in the tumor microenvironment (TME) allowed the development of effective drugs: in particular, monoclonal antibodies targeting the so-called immune checkpoint molecules yielded striking and lasting effects in some tumors. Unfortunately, these monoclonal antibodies are not effective in a majority of patients and are ineffective in several solid malignancies. Furthermore, due to their mechanism of action, checkpoint inhibitors often elicit autoimmune-like disease.Main bodyThe use of viruses as oncolytic agents (OVs) was considered in the past, while only recently OVs revealed a connection with immunotherapy. However, their antitumoral potential has remained largely unexplored, due to safety concerns and some limitations in the techniques to manipulate viruses. OV research was recently revived by a better knowledge of viral/cancer biology and advances in the methodologies to delete virulence/immune-escape related genes from even complex viral genomes or "to arm" OVs with appropriate transgenes. Recently, the first oncolytic virus, the HSV-1 based Talimogene Laherparepvec (T-VEC), was approved for the treatment of non-resectable melanoma in USA and Europe.ConclusionOVs have the potential to become powerful agents of cancer immune and gene therapy. Indeed, in addition to their selective killing activity, they can act as versatile gene expression platforms for the delivery of therapeutic genes. This is particularly true for viruses with a large DNA genome, that can be manipulated to address the multiple immunosuppressive features of the TME. This review will focus on the open issues, on the most promising lines of research in the OV field and, more in general, on how OVs could be improved to achieve real clinical breakthroughs in cancers that are usually difficult to treat by immunotherapy.

Dataset Information

NF-?B Signaling in Targeting Tumor Cells by Oncolytic Viruses-Therapeutic Perspectives.

Publications

NF-κB Signaling in Targeting Tumor Cells by Oncolytic Viruses-Therapeutic Perspectives.

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