Related Experiment Video
Updated: Jun 11, 2025
Monitoring of Nanodrug Accumulation in Murine Breast Cancer Metastases
Published on: August 23, 2024
Prospects for breast cancer immunotherapy using microRNAs and transposable elements as objects
1Department of Medical Genetics and Fundamental Medicine, Bashkir State Medical University, Ministry of Health of Russia, 450008 Ufa, Russia.
Abstract:
One of the directions in treatment of chemoresistant breast cancer (BC) may include new methods of activating the immune response against tumor cells. Clinically used checkpoint inhibition using antibodies to PD-1 and PD-L1 works in some patients, but the lack of biomarkers means number of respondents is low. The possibility of combining this method with chemotherapy is limited by an increased risk of toxic liver damage, development of immune-related pneumonitis, and thyroid dysfunction. This article includes introduction into the clinic of new methods of immunotherapy for BC, among which epigenetic activation of retroelements, double-stranded transcripts of which stimulate the interferon response against the tumor, is promising. For this purpose, inhibitors of DNA methyltransferase*, histone deacetylase* and histone methyltransferase* are used (* subtitles in the main text). Their antitumor effect is also mediated by removal of repressive epigenetic marks from tumor suppressor genes. However, numerous studies have proven the role of retroelements in the carcinogenesis of various malignant neoplasms, including BC. Moreover, endogenous retroviruses HERV-K and LINE1 retrotransposons are planned to be used as diagnostic biomarkers for BC. Therefore, a rational approach to using viral mimicry in antitumor therapy of BC may be the simultaneous suppression of specific retrotransposons (drivers for carcinogenesis) using reverse transcriptase inhibitors and silencing of specific transposons involved in carcinogenesis using complementary microRNAs. To determine possible pathways of influence in this direction, 35 specific transposon-derived microRNAs* changes in BC were identified, which can become guides for targeted therapy of BC.
Insights
New immunotherapy strategies for chemoresistant breast cancer (BC) involve epigenetic activation of retroelements to boost immune response. This approach, alongside targeted microRNA therapy, offers a promising avenue for treating difficult-to-manage BC cases.
Area of Science:
- Oncology
- Immunotherapy
- Epigenetics
Background:
- Chemoresistant breast cancer (BC) poses a significant clinical challenge, with limited efficacy of current immunotherapies like checkpoint inhibitors (PD-1/PD-L1) due to lack of biomarkers and potential toxicities.
- Retroelements, including endogenous retroviruses (HERV-K) and LINE1 retrotransposons, play a dual role in BC, contributing to carcinogenesis while also offering potential as diagnostic biomarkers.
- Current treatment limitations necessitate novel therapeutic strategies for BC, particularly for chemoresistant forms.
Purpose of the Study:
- To explore novel immunotherapy approaches for chemoresistant breast cancer (BC) by leveraging epigenetic modifications and retroelement activation.
- To investigate the potential of using viral mimicry strategies, including retroelement manipulation, for enhancing antitumor immune responses in BC.
- To identify specific microRNAs associated with transposon activity for targeted BC therapy.
Main Methods:
- Epigenetic activation of retroelements using inhibitors of DNA methyltransferase, histone deacetylase, and histone methyltransferase to stimulate interferon response against tumor cells.
- Utilizing reverse transcriptase inhibitors to suppress specific oncogenic retrotransposons and complementary microRNAs to silence others involved in BC carcinogenesis.
- Identification of 35 specific transposon-derived microRNA changes in BC to guide targeted therapy development.
Main Results:
- Epigenetic modification strategies can activate retroelements, leading to an enhanced immune response against tumor cells.
- Retroelements are implicated in BC carcinogenesis and are being explored as diagnostic biomarkers.
- Specific microRNA alterations associated with transposon activity in BC have been identified as potential therapeutic targets.
Conclusions:
- Epigenetic activation of retroelements presents a promising immunotherapy strategy for chemoresistant breast cancer.
- Simultaneous suppression of oncogenic retrotransposons and silencing of specific transposons via microRNAs offers a rational approach for BC treatment.
- Identified transposon-derived microRNAs can serve as guides for developing targeted therapies for breast cancer.
