The immunomodulatory anticancer agent, RRx-001, induces an interferon response through epigenetic induction of viral mimicry
详细信息 查看全文
- 作者：Hongjuan Zhao ; Shoucheng Ning ; Rosalie Nolley ; Jan Scicinski…
- 关键词：Epigenetics ; Cancer ; RRx ; 001 ; Interferon response ; Viral mimicry ; Pseudo ; infection
- 刊名：Clinical Epigenetics
- 出版年：2017
- 出版时间：December 2017
- 年：2017
- 卷：9
- 期：1
- 全文大小：2673KB
- 刊物主题：Human Genetics; Gene Function;
- 出版者：BioMed Central
- ISSN：1868-7083
- 卷排序：9
文摘
BackgroundRRx-001, a dinitroazetidine derivative, is a novel anticancer agent currently in phase II clinical trials. It mediates immunomodulatory effects either directly through polarization of tumor associated macrophages or indirectly through vascular normalization and increased T-lymphocyte infiltration. With multiple additional mechanisms of action including upregulation of oxidative stress, depletion of GSH and NADPH, anti-angiogenesis and epigenetic modulation, RRx-001 is being studied as a radio- and chemo-sensitizer to resensitize tumors to prior therapy and to prime tumors to respond to radiation, chemotherapy and immunotherapy in combination therapy studies. Here, we identified another mechanism, viral mimicry, which refers to the “unsilencing” of epigenetically repressed viral genes present in the tumor that provokes an immune response and may contribute to the anticancer activity of RRx-001.