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Updated: Sep 23, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
PRMT inhibition induces a viral mimicry response in triple-negative breast cancer
Qin Wu1, David Y Nie2,3,4, Wail Ba-Alawi3,4
1The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China. wuqin@ibmc.ac.cn.
Abstract:
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis and few effective therapies. Here we identified MS023, an inhibitor of type I protein arginine methyltransferases (PRMTs), which has antitumor growth activity in TNBC. Pathway analysis of TNBC cell lines indicates that the activation of interferon responses before and after MS023 treatment is a functional biomarker and determinant of response, and these observations extend to a panel of human-derived organoids. Inhibition of type I PRMT triggers an interferon response through the antiviral defense pathway with the induction of double-stranded RNA, which is derived, at least in part, from inverted repeat Alu elements. Together, our results represent a shift in understanding the antitumor mechanism of type I PRMT inhibitors and provide a rationale and biomarker approach for the clinical development of type I PRMT inhibitors.
Insights
MS023, a type I protein arginine methyltransferase (PRMT) inhibitor, shows antitumor activity in triple-negative breast cancer (TNBC). It triggers an interferon response, offering a new therapeutic strategy and biomarker for TNBC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options.
- Type I protein arginine methyltransferases (PRMTs) are implicated in cancer progression.
Purpose of the Study:
- To investigate the antitumor activity of MS023, a type I PRMT inhibitor, in TNBC.
- To identify biomarkers and understand the mechanism of response to type I PRMT inhibitors in TNBC.
Main Methods:
- Treatment of TNBC cell lines and organoids with MS023.
- Pathway analysis to assess molecular changes.
- Interferon response and double-stranded RNA induction analysis.
Main Results:
- MS023 demonstrated significant antitumor growth activity in TNBC models.
- Activation of interferon responses was identified as a biomarker for MS023 efficacy.
- MS023 treatment induced interferon responses via antiviral pathways and double-stranded RNA, partly from Alu elements.
Conclusions:
- Type I PRMT inhibition triggers an interferon response, representing a novel antitumor mechanism in TNBC.
- MS023 offers a potential therapeutic strategy for TNBC.
- Interferon response serves as a predictive biomarker for type I PRMT inhibitor therapy in TNBC.
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