Targeting IFN/STAT1 Pathway as a Promising Strategy to Overcome Radioresistance

Onco Targets Ther. 2020 Jun 24:13:6037-6050. doi: 10.2147/OTT.S256708. eCollection 2020.

Abstract

The interferon (IFN)-mediated activation of the Janus kinase (JAK)-signal transducer and activator of transcription 1 (STAT1) signaling is crucial for cell sensitivity to ionizing radiation. Several preclinical studies have reported that the IFN/STAT1 pathway mediates radioresistance in the tumor microenvironment by shielding the immune responses and activating survival signaling pathways. This review focuses on the oncogenic function of the IFN/STAT1 pathway, emphasizing the major signaling pathway in radiation sensitization. Furthermore, it highlights the possibility of mediatory roles of the IFN/STAT1 pathway as a prognostic therapeutic target in the modulation of resistance to radiotherapy and chemotherapy. MicroRNA involved in the regulation of the IFN/STAT1 pathway is also discussed. A better understanding of radiation-induced IFN/STAT1 signaling will open new opportunities for the development of novel therapeutic strategies, as well as define new approaches to enhance radio-immunotherapy efficacy in the treatment of various types of cancers.

Keywords: IFN/STAT1; interferon-gamma signaling; microRNA; signal transducer and activator of transcription 1; tumor radioresistance.

Publication types

  • Review