Research ArticleCancer

Dimethyl fumarate potentiates oncolytic virotherapy through NF-κB inhibition

See allHide authors and affiliations

Science Translational Medicine  24 Jan 2018:
Vol. 10, Issue 425, eaao1613
DOI: 10.1126/scitranslmed.aao1613

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

A virus’s little helper

Oncolytic viruses, which kill cancer cells, can offer an effective and versatile approach for treating cancer. However, they need to reach tumor cells and get inside them to achieve a therapeutic effect, and this does not always happen. Selman et al. identified a promising solution for this problem by combining oncolytic vesicular stomatitis virus with dimethyl fumarate, a small-molecule drug that is already in use for some nonmalignant disorders and may also have direct anticancer effects. Dimethyl fumarate promoted viral infection of cancer cells, and the combined treatment was effective in multiple cancer models, including those that did not respond to virus or drug treatment alone.

Abstract

Resistance to oncolytic virotherapy is frequently associated with failure of tumor cells to get infected by the virus. Dimethyl fumarate (DMF), a common treatment for psoriasis and multiple sclerosis, also has anticancer properties. We show that DMF and various fumaric and maleic acid esters (FMAEs) enhance viral infection of cancer cell lines as well as human tumor biopsies with several oncolytic viruses (OVs), improving therapeutic outcomes in resistant syngeneic and xenograft tumor models. This results in durable responses, even in models otherwise refractory to OV and drug monotherapies. The ability of DMF to enhance viral spread results from its ability to inhibit type I interferon (IFN) production and response, which is associated with its blockade of nuclear translocation of the transcription factor nuclear factor κB (NF-κB). This study demonstrates that unconventional application of U.S. Food and Drug Administration–approved drugs and biological agents can result in improved anticancer therapeutic outcomes.

View Full Text