Radiotherapy and radiosensitization in breast cancer: Molecular targets and clinical applications. (January 2022)

• Record Type: Journal Article
• Authors: Bhat, Vasudeva; Pellizzari, Sierra; Allan, Alison L.; Wong, Eugene; Lock, Michael; Brackstone, Muriel; Lohmann, Ana Elisa; Cescon, David W.; Parsyan, Armen
• Is Part Of: Critical reviews in oncology/hematology. Volume 169(2022)
• Publication Date: 2022-01
• Subjects: ER Estrogen receptor -- PR Progesterone receptor -- HER2 Human epidermal growth factor 2 -- RT Radiotherapy -- CDK4/6 Cyclin-dependent kinase 4/6 -- TNBC Triple-negative breast cancer -- PARP Poly (ADP-ribose) polymerase -- PD-L1 Programmed death-ligand 1 -- SABR Stereotactic ablative radiotherapy -- ROS Reactive oxygen species -- DSB Double-strand breaks -- DDR DNA damage repair -- ATM Ataxia telangiectasia-mutated -- ATR Ataxia telangiectasia and Rad3-related -- NHEJ Non-homologous end joining -- HR Homologous repair -- HIF-1 Hypoxia-inducible factor 1 -- IFN Interferon -- DNA-PKcs DNA-dependent protein kinase catalytic subunit -- HJURP Holliday junction recognition protein -- GARD Genome-adjusted radiation dose -- 5-FU 5-flurouracil -- STAT3 signal transducer and activators of transcription 3 -- KDM5B Lysine specific demethylase 5B -- TNF Tumor necrosis factor; Breast cancer -- Combination therapy -- Radiotherapy -- Chemotherapy -- Radioresistance -- Radiosensitizers; Oncology -- Periodicals; Hematology -- Periodicals; 616.994
• DOI: 10.1016/j.critrevonc.2021.103566
• Languages: English
• ISSNs: 1040-8428

Abstract

Graphical abstract: Highlights: Enhancing effects of radiotherapy by using radiosensitizing agents is a promising strategy in breast cancer treatment. Various drugs for breast cancer show properties of radiosensitizers in preclinical and early stage clinical studies. Biomarkers for radiosensitivity in breast cancer are lacking, despite a number of promising molecular targets. Abstract: Relatively poor survival outcomes are observed in advanced or metastatic breast cancer, where local control of the primary or metastatic disease may be achieved by surgical resection, local ablative and radiation therapies. Radioresistance, poses a major challenge in achieving durable oncologic outcomes, mandating development of novel management strategies. Although multimodality approaches that combine radiotherapy with chemotherapy, or systemic agents, are utilized for radiosensitization and treatment of various malignancies, this approach has not yet found its clinical application in breast cancer. Some agents for breast cancer treatment can serve as radiosensitizers, creating an opportunity to enhance effects of radiation while providing systemic disease control. Hence, combination of radiotherapy with radiosensitizing agents have the potential to improve oncologic outcomes in advanced or metastatic breast cancer. This review discusses molecular targets for radiosensitization and novel systemic agents that have potential for clinical use as radiosensitizers in breast cancer.