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Targeting Oestrogen Receptor Signalling in Breast Cancer Therapy.
Adv 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.
View Article and Find Full Text PDFERα dysfunction caused by ESR1 mutations and therapeutic pressure promotes lineage plasticity in ER breast cancer.
Nat Cancer
January 2025
Department of Discovery Oncology, Genentech, South San Francisco, CA, USA.
Multiple next-generation molecules targeting estrogen receptor α (ERα) are being investigated in breast cancer clinical trials, encompassing thousands of women globally. Development of these molecules was partly motivated by the discovery of resistance-associated mutations in ESR1 (encodes ERα). Here, we studied the impact of ERα antagonist/degraders against Esr1 mutations expressed in mouse mammary glands.
View Article and Find Full Text PDFAlginate oligosaccharides relieve estrogen-deprived osteosarcopenia by affecting intestinal Th17 differentiation and systemic inflammation through the manipulation of bile acid metabolism.
Int J Biol Macromol
January 2025
Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China. Electronic address:
Alginate oligosaccharides (AOS) have gained attention for their capacity to regulate human health as prebiotics. Osteosarcopenia is a progressive disease of the musculoskeletal system and result in heavy burden of patients. Studies suggest that gut microbiota is involved in the pathogenesis of osteosarcopenia, whether AOS can improve the symptoms of osteosarcopenia by modulating gut microbiota remains to be elucidated.
View Article and Find Full Text PDFAngelica gigas Nakai (Korean Dang-gui) Root Alcoholic Extracts in Health Promotion and Disease Therapy - active Phytochemicals and In Vivo Molecular Targets.
Pharm Res
January 2025
Penn State Cancer Institute, Pennsylvania State University, Hershey, PA, 17033, USA.
Angelica gigas Nakai (AGN) root is a medicinal herbal widely used in traditional medicine in Korea. AGN root ethanolic extracts have been marketed as dietary supplements in the United States for memory health and pain management. We have recently reviewed the pharmacokinetics (PK) and first-pass hepatic metabolism of ingested AGN supplements in humans for the signature pyranocoumarins decursin (D, C 1x), decursinol angelate (DA, C ~ 10x) and their common botanical precursor and hepatic metabolite decursinol (DOH, C ~ 1000x).
View Article and Find Full Text PDFOxidative Phosphorylation is a Metabolic Vulnerability of Endocrine Therapy-Tolerant Persister Cells in ER+ Breast Cancer.
Cancer Res
January 2025
Medical College of Wisconsin, Milwaukee, WI, United States.
Despite adjuvant treatment with endocrine therapies, estrogen receptor-positive (ER+) breast cancers recur in a significant proportion of patients. Recurrences are attributable to clinically undetectable endocrine-tolerant persister cancer cells that retain tumor-forming potential. Therefore, strategies targeting such persister cells may prevent recurrent disease.
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