Table 3 Preclinical studies of OV combining with small molecule epigenetic drugs

AdV:

H101

TSA

Esophageal squamous cell carcinoma

1). Enhance viral replication and spread. 2). Improved antitumor activity

Ma, 2017 [236]

Herpes virus:

GM-CSF-HSV

VPA

(valproic acid)

(In vitro)

1). VPA enhances viral replication and GM-CSF production and oncolysis; 2). VPA improves antitumor immunity.

Jennings, 2019 [237]

BHV-1

Trichostatin A (TSA)

Lung cancer

1). TSA promotes viral replication; 2). TSA exacerbates DNA damage and cytopathology, suggesting a synergy between BHV-1 and TSA

Qiu, 2021 [238]

Rhabdoviridae:

VSVΔM51

Vorinostat; MS275; SIRTi

Prostate cancer

1). SIRT1 inhibition promotes the permissivity of prostate cancer PC-3 cells to VSVΔM51 replication and oncolysis; 2). HDACi upregulated the microRNA miR-34a that regulated the level of SIRT1.

Muscolini, 2019 [239]

Reoviridae (RV):

Reolysin

Entinostat

Vorinostat

1). Squamous cell carcinoma.

2). Multiple myeloma

1). HDAC inhibition increased JAM-1 and reovirus entry, and viral replication; 2). The combination results in synergistic killing via apoptosis; 3). The combination improved immune cell infiltration and higher therapeutic efficacy.

Jaime-Ramirez, 2017 [240]

Stiff, 2016 [241]

Reolysin

belinostat

Lymphoma

1). Belinostat-resistant lymphoma cell exhibit downregulated IRF1 and STAT1 expression; 2). These cells are hypersensitive to RV replication and induced cell death; 3). The combination therapy displays synergy.

Islam, 2020 [242]

Paramyxoviridae: MeV

Resminostat

Pancreatic cancer

1). Synergistic mode of cytotoxicity.

2). The HDACi neither impaired MeV growth kinetics nor prevented the activation of the interferon signaling pathway.

Ellerhoff, 2016 [243]

Parvoviridae:

P/V-CP

Scripaid

Small cell lung cancer cells/laryngeal carcinoma cells

1). enhanced spread of the virus and cell apoptosis; 2). suppressed interferon-beta induction through blocking phosphorylation and nuclear translocation of IRF-3.

Fox, 2019 [244]