Estrogens exert a plethora of actions conducted to brain preservation and functioning. Some of these actions are initiated in lipid rafts, which are particular microstructures of the plasma membrane. Preservation of lipid raft structure in neurons is essential for signal transduction against different injuries, such as Alzheimer's disease (AD). These membrane structures appear to be disrupted as this neuropathology evolves, and that may largely contribute to dysfunction of raft resident proteins involved in intracellular signalling. This review includes a survey of some protein interactions that are involved in the structural maintenance and signal transduction mechanisms for neuronal survival against AD. Particularly relevant are the rapid mechanisms developed by estrogen to prevent neuronal death, through membrane estrogen receptors (mER) interactions with a voltage-dependent anion channel (VDAC) and other protein markers within neuronal lipid rafts. These interactions may have important consequences in estrogen mechanisms to achieve neuroprotection against amyloid beta (Abeta-induced toxicity).
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http://dx.doi.org/10.2741/471 | DOI Listing |
Breast Cancer Res
January 2025
Department of Cancer Biology, Loyola University Chicago Stritch School of Medicine, Maywood, IL, 50153, USA.
Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations to estrogen receptor alpha (ERα) arise after continued therapeutic pressure. Next generation selective estrogen receptor modulators and degraders/downregulators (SERMs and SERDs) show clinical efficacy, but responses are often non-durable.
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January 2025
Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi Province, China.
The benefit of adjuvant chemotherapy (CT) for hormone receptor-negative T1a and T1bN0M0 breast cancer remains uncertain. Our study was to explore prognostic value and identify candidates of adjuvant CT for these patients. The data of hormone receptor-negative T1a and T1bN0M0 breast cancer patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015.
View Article and Find Full Text PDFAdv Exp Med Biol
January 2025
Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
HER2-positive (+) breast cancer is an aggressive disease with poor prognosis, a narrative that changed drastically with the advent and approval of trastuzumab, the first humanized monoclonal antibody targeting HER2. In addition to another monoclonal antibody, more classes of HER2-targeted agents, including tyrosine kinase inhibitors, and antibody-drug conjugates were developed in the years that followed. While these potent therapies have substantially improved the outcome of patients with HER2+ breast cancer, resistance has prevailed as a clinical challenge ever since the arrival of targeted agents.
View Article and Find Full Text PDFAdv Exp Med Biol
January 2025
Translational Research Unit, Hospital of Prato, AUSL Toscana Centro, Prato, Italy.
The cyclin-dependent kinases 4 and 6 inhibitors are the mainstay of treatment for patients with hormone receptor-positive and HER2-negative breast cancer. The ability of these drugs to improve the outcome of patients both in the metastatic and the early setting has been largely demonstrated. However, resistance, either de novo or acquired, represents a major clinical challenge.
View Article and Find Full Text PDFAdv Exp Med Biol
January 2025
Division of Cancer Sciences, University of Manchester, Manchester, UK.
There has been over 130 years of research into the treatment of breast cancer using approaches that target oestrogen receptor signalling. Here, we summarise the development of the key pillars of such endocrine therapy, namely, oestrogen deprivation, achieved through ovarian suppression and/or aromatase inhibition, and oestrogen receptor blockade, through selective oestrogen receptor modulators, downregulators and novel compounds entering early phase development. The translation of these compounds from advanced to early breast cancer settings is discussed with a focus on the placebo-controlled breast cancer prevention studies to most accurately describe the side effect profiles of the main approaches.
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