title: Pushing estrogen receptor around in breast cancer.
abstract: The estrogen receptor-α (herein called ER) is a nuclear sex steroid receptor (SSR) that is expressed in approximately 75% of breast cancers. Therapies that modulate ER action have substantially improved the survival of patients with ER-positive breast cancer, but resistance to treatment still remains a major clinical problem. Treating resistant breast cancer requires co-targeting of ER and alternate signalling pathways that contribute to resistance to improve the efficacy and benefit of currently available treatments. Emerging data have shown that other SSRs may regulate the sites at which ER binds to DNA in ways that can powerfully suppress the oncogenic activity of ER in breast cancer. This includes the progesterone receptor (PR) that was recently shown to reprogram the ER DNA binding landscape towards genes associated with a favourable outcome. Another attractive candidate is the androgen receptor (AR), which is expressed in the majority of breast cancers and inhibits growth of the normal breast and ER-positive tumours when activated by ligand. These findings have led to the initiation of breast cancer clinical trials evaluating therapies that selectively harness the ability of SSRs to 'push' ER towards anti-tumorigenic activity. Our review will focus on the established and emerging clinical evidence for activating PR or AR in ER-positive breast cancer to inhibit the tumour growth-promoting functions of ER.
authors.affiliation: Garvan Institute of Medical Research and St Vincent's HospitalUniversity of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Elgene
authors.initials: E
authors.lastname: Lim
authors.affiliation: Dame Roma Mitchell Cancer Research Laboratories and Adelaide Prostate Cancer Research CentreUniversity of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Gerard
authors.initials: G
authors.lastname: Tarulli
authors.affiliation: Garvan Institute of Medical Research and St Vincent's HospitalUniversity of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Neil
authors.initials: N
authors.lastname: Portman
authors.affiliation: Dame Roma Mitchell Cancer Research Laboratories and Adelaide Prostate Cancer Research CentreUniversity of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Theresa E
authors.initials: TE
authors.lastname: Hickey
authors.affiliation: Dame Roma Mitchell Cancer Research Laboratories and Adelaide Prostate Cancer Research CentreUniversity of Adelaide, Adelaide, South Australia, Australia wayne.tilley@adelaide.edu.au c.palmieri@liverpool.ac.uk.
authors.forename: Wayne D
authors.initials: WD
authors.lastname: Tilley
authors.affiliation: Institute of Translational MedicineUniversity of Liverpool, Clatterbridge Cancer Centre, NHS Foundation Trust, and Royal Liverpool University Hospital, Liverpool, Merseyside, UK wayne.tilley@adelaide.edu.au c.palmieri@liverpool.ac.uk.
authors.forename: Carlo
authors.initials: C
authors.lastname: Palmieri
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods* / Q000639:trends; D011944:Receptors, Androgen / Q000502:physiology*; D011960:Receptors, Estrogen / Q000502:physiology*; D011980:Receptors, Progesterone / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C410798:AR protein, human; D018931:Antineoplastic Agents, Hormonal; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone
keywords: androgen receptor; breast cancer; endocrine resistance; endocrine therapy; estrogen receptor; progesterone receptor