Abstract
Numerous studies have established a proof of concept that abnormal expression and function of estrogen receptors (ER) are crucial processes in initiation and development of hormone-related cancers and also affect the efficacy of anti-cancer therapy. Radiotherapy has been applied as one of the most common and potent therapeutic strategies, which is synergistic with surgical excision, chemotherapy and targeted therapy for treating malignant tumors. However, the impact of ionizing radiation on ER expression and ER-related signaling in cancer tissue, as well as the interaction between endocrine and irradiation therapy remains largely elusive. This review will discuss recent findings on ER and ER-related signaling, which are relevant for cancer radiotherapy. In addition, we will summarize pre-clinical and clinical studies that evaluate the consequences of anti-estrogen and irradiation therapy in cancer, including emerging studies on head and neck cancer, which might improve the understanding and development of novel therapeutic strategies for estrogen-related cancers.
Highlights
Estrogens exert many physiological functions in target tissues mainly via two members of the nuclear receptor superfamily: Estrogen receptor-α (ERα) and ERβ. They are encoded by separate genes, ESR1 and ESR2, respectively, transcribed from various chromosomal locations, and multiple mRNA splice variants exist for both receptors in normal and disease states [1,2]
non-homologous end jointing (NHEJ) is considered as the primary double strand breaks (DSB) repair pathway, which is activated throughout the cell cycle and relies on rejoining free DNA ends without the requirement for sequence homology
It is worth noting that estrogens have been shown to induce components of NHEJ in breast cancer cells and that therapeutic targeting of estrogen receptors (ER) result in irreparable DSB [22]
Summary
Estrogens exert many physiological functions in target tissues mainly via two members of the nuclear receptor superfamily: Estrogen receptor-α (ERα) and ERβ. They are encoded by separate genes, ESR1 and ESR2, respectively, transcribed from various chromosomal locations, and multiple mRNA splice variants exist for both receptors in normal and disease states [1,2]. Radiotherapy is used as one of the most common and potent cancer therapeutic strategies It acts synergistically with surgical excision, chemotherapy and targeted therapy for treating malignant tumors in human. The variability of ERα and ERβ expression, diverse response of ER and ER-related signaling to irradiation both contribute to the risk of safety and efficacy of cancer therapy. We will summarize pre-clinical and clinical studies that evaluate the consequences of anti-estrogen and irradiation therapy in cancer, including emerging studies on head and neck cancer, which might improve the understanding and development of novel therapeutic strategies for estrogen-related cancers
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