Estrogen Receptor Signaling in Radiotherapy: From Molecular Mechanisms to Clinical Studies

Int J Mol Sci. 2018 Mar 2;19(3):713. doi: 10.3390/ijms19030713.

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.

Keywords: breast cancer; estrogen; estrogen receptor; head and neck cancer; radioresistance; radiotherapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / etiology
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / radiotherapy
  • Combined Modality Therapy
  • Estrogens / metabolism
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Head and Neck Neoplasms / etiology
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / therapy
  • Humans
  • Protein Binding
  • Radiation, Ionizing
  • Radiotherapy
  • Receptors, Estrogen / antagonists & inhibitors
  • Receptors, Estrogen / chemistry
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Signal Transduction* / radiation effects

Substances

  • Antineoplastic Agents
  • Estrogens
  • Receptors, Estrogen