Dr. Simon Langdon E-Mail
Reader, School of Medicine, University of Edinburgh, Edinburgh, UK
Research Keywords: ovarian cancer; breast cancer; estrogen signaling; HER signaling; DNA repair
Dr. Valerie Speirs E-Mail
Professor and Chair in Molecular Oncology, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK
Research Keywords: oestrogen receptor biology; endocrine resistant breast cancer; male breast cancer; in vitro models; biomarker
The majority of breast cancers are estrogen receptor alpha (ERa) positive and most will initially respond to endocrine therapy. Current therapies to treat ERa-positive disease include aromatase inhibitors, selective estrogen receptor modulators (SERMs) and selective estrogen down-regulators (SERDs). However, resistance to these treatments will develop in many cancers and can be present either at the outset (de novo resistance) or develop on treatment (acquired resistance). Experimental and clinical investigations have demonstrated multiple mechanisms that can give rise to resistance and a range of therapeutic agents such as CDK4/6 inhibitors and other signalling inhibitors have been developed to circumvent these. Resistance mechanisms include changes in ER status (e.g. loss and mutation) and the involvement of compensatory pathways bypassing the dependence on estrogen activation particularly growth factor activation.
In this issue, we welcome Reviews and Original Articles encompassing experimental laboratory research studies of endocrine resistance through to clinical investigations in breast cancer.
Keywords: Breast cancer; resistance; endocrine; estrogen
Adjuvant hormonal therapy is one of the most important treatments of hormone-receptor-positive breast cancer and includes selective estrogen receptor modulators, aromatase inhibitors, and luteinizing hormone-releasing hormone analogs. In patients receiving these drugs, a progressive recession of frontal-temporal hairlines is often observed, such as a certain grade of hair miniaturization in the same areas and the central scalp area, producing a pseudo-female androgenic alopecia, which has to be considered oncotherapy-induced alopecia. The aim of this work, is to describe the clinical aspects and pathogenesis of this type of alopecia and to analyze the different drugs which have been proposed until now. The authors concude that topical hormones should not be considered as a therapeutic approach because of their direct or indirect oncogenic potential. A therapeutic approach that could be both safe and effective is proposed.
Breast cancer (BC) is the most ubiquitous cancer in women. Approximately 70–80% of BC diagnoses are positive for estrogen receptor (ER) alpha (ERα). The steroid hormone estrogen [17β-estradiol (E2)] plays a vital role both in the initiation and progression of BC. The E2-ERα mediated actions involve genomic signaling and non-genomic signaling. The specificity and magnitude of ERα signaling are mediated by interactions between ERα and several coregulator proteins called coactivators or corepressors. Alterations in the levels of coregulators are common during BC progression and they enhance ligand-dependent and ligand-independent ERα signaling which drives BC growth, progression, and endocrine therapy resistance. Many ERα coregulator proteins function as scaffolding proteins and some have intrinsic or associated enzymatic activities, thus the targeting of coregulators for blocking BC progression is a challenging task. Emerging data from in vitro and in vivo studies suggest that targeting coregulators to inhibit BC progression to therapy resistance is feasible. This review explores the current state of ERα coregulator signaling and the utility of targeting the ERα coregulator axis in treating advanced BC.