Nina Radosevic-Robin1, Yazid Belkacemi2,3,4, Nhu Hanh To5,6, Hoang Quy Nguyen7, Allan Thiolat8,6, Bisheng Liu5, José Cohen8,6. 1. Department of Pathology, Centre Jean Perrin, University Clermont Auvergne, INSERM U1240, Clermont-Ferrand, France. 2. Radiation Oncology Department and Henri Mondor Breast Center, AP-HP, Henri Mondor University Hospital, 1 rue Gustave Eiffel, 94010, Créteil, France. yazid.belkacemi@aphp.fr. 3. University of Paris-Est Créteil (UPEC), Créteil, France. yazid.belkacemi@aphp.fr. 4. INSERM Unit 955, Immunoregulation and Biotherapy (I-Biot) Team, Mondor Institute of Biomedical Research (IMRB), Créteil, France. yazid.belkacemi@aphp.fr. 5. Radiation Oncology Department and Henri Mondor Breast Center, AP-HP, Henri Mondor University Hospital, 1 rue Gustave Eiffel, 94010, Créteil, France. 6. INSERM Unit 955, Immunoregulation and Biotherapy (I-Biot) Team, Mondor Institute of Biomedical Research (IMRB), Créteil, France. 7. Department of Medical Oncology 4, Ho Chi Minh City Oncology Hospital, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam. 8. University of Paris-Est Créteil (UPEC), Créteil, France.
Abstract
PURPOSE: Radiation therapy (RT) for triple-negative breast cancer (TNBC) treatment is currently delivered in the adjuvant setting and is under investigation as a booster of neoadjuvant treatments. However, TNBC radioresistance remains an obstacle, so new biomarkers are needed to select patients for any integration of RT in the TNBC therapy sequence. MicroRNAs (miRs) are important regulators of gene expression, involved in cancer response to ionizing radiation (IR) and assessable by tumor tissue or liquid biopsy. This systematic review aimed to evaluate the relationships between miRs and response to radiation in TNBC, as well as their potential predictive and prognostic values. METHODS: A thorough review of studies related to miRs and RT in TNBC was performed on PubMed, EMBASE, and Web of Science. We searched for original English articles that involved dysregulation of miRs in response to IR on TNBC-related preclinical and clinical studies. After a rigorous selection, 44 studies were chosen for further analysis. RESULTS: Thirty-five miRs were identified to be TNBC related, out of which 21 were downregulated, 13 upregulated, and 2 had a double-side expression in this cancer. Expression modulation of many of these miRs is radiosensitizing, among which miR-7, -27a, -34a, -122, and let-7 are most studied, still only in experimental models. The miRs reported as most influencing/reflecting TNBC response to IR are miR-7, -27a, -155, -205, -211, and -221, whereas miR-21, -33a, -139-5p, and -210 are associated with TNBC patient outcome after RT. CONCLUSION: miRs are emerging biomarkers and radiosensitizers in TNBC, worth further investigation. Dynamic assessment of circulating miRs could improve monitoring and TNBC RT efficacy, which are of particular interest in the neoadjuvant and the high-risk patients' settings.
PURPOSE: Radiation therapy (RT) for triple-negative breast cancer (TNBC) treatment is currently delivered in the adjuvant setting and is under investigation as a booster of neoadjuvant treatments. However, TNBC radioresistance remains an obstacle, so new biomarkers are needed to select patients for any integration of RT in the TNBC therapy sequence. MicroRNAs (miRs) are important regulators of gene expression, involved in cancer response to ionizing radiation (IR) and assessable by tumor tissue or liquid biopsy. This systematic review aimed to evaluate the relationships between miRs and response to radiation in TNBC, as well as their potential predictive and prognostic values. METHODS: A thorough review of studies related to miRs and RT in TNBC was performed on PubMed, EMBASE, and Web of Science. We searched for original English articles that involved dysregulation of miRs in response to IR on TNBC-related preclinical and clinical studies. After a rigorous selection, 44 studies were chosen for further analysis. RESULTS: Thirty-five miRs were identified to be TNBC related, out of which 21 were downregulated, 13 upregulated, and 2 had a double-side expression in this cancer. Expression modulation of many of these miRs is radiosensitizing, among which miR-7, -27a, -34a, -122, and let-7 are most studied, still only in experimental models. The miRs reported as most influencing/reflecting TNBC response to IR are miR-7, -27a, -155, -205, -211, and -221, whereas miR-21, -33a, -139-5p, and -210 are associated with TNBC patient outcome after RT. CONCLUSION: miRs are emerging biomarkers and radiosensitizers in TNBC, worth further investigation. Dynamic assessment of circulating miRs could improve monitoring and TNBC RT efficacy, which are of particular interest in the neoadjuvant and the high-risk patients' settings.
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