Journal ArticleDOI
Advanced concepts in estrogen receptor biology and breast cancer endocrine resistance: implicated role of growth factor signaling and estrogen receptor coregulators.
Rachel Schiff,Suleiman Massarweh,Jiang Shou,Lavina Bharwani,Grazia Arpino,Mothaffar F. Rimawi,C. Kent Osborne +6 more
TLDR
Compelling experimental and clinical evidence suggest that the epidermal growth factor/her2/neu receptor (EGFR/HER2) pathway might play a distinct role in endocrine resistance, and especially in resistance to selective estrogen receptor modulators (SERMs) such as tamoxifen.Abstract:
Estrogen receptor (ER), mediating estrogen-signaling stimuli, is a dominant regulator and a key therapeutic target in breast cancer etiology and progression. Endocrine therapy, blocking the ER pathway, is one of the most important systemic therapies in breast cancer management, but de novo and acquired resistance is still a major clinical problem. New research highlights the role of both genomic and nongenomic ER activities and their intimate molecular crosstalk with growth factor receptor and other signaling kinase pathways in endocrine resistance. These signaling pathways, when overexpressed and/or hyperactivated, can modulate both activities of ER, resulting in endocrine resistance. Thus, these signal transduction receptors and signaling molecules may serve as both predictive markers and novel therapeutic targets to circumvent endocrine resistance. Compelling experimental and clinical evidence suggest that the epidermal growth factor/HER2/neu receptor (EGFR/HER2) pathway might play a distinct role in endocrine resistance, and especially in resistance to selective estrogen receptor modulators (SERMs) such as tamoxifen. Results from preclinical studies of treatment combinations with various endocrine therapy drugs together with several potent anti-EGFR/HER2 inhibitors are very promising, and clinical trials to see whether this new strategy is effective in patients are now ongoing.read more
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Journal ArticleDOI
Estrogen Receptors: How Do They Signal and What Are Their Targets
Nina Heldring,Ashley C. W. Pike,Sandra Andersson,Jason Matthews,Guojun Cheng,Johan Hartman,Michel Tujague,Anders Ström,Eckardt Treuter,Margaret Warner,Jan-Åke Gustafsson +10 more
TL;DR: This review focuses on several of the interesting recent discoveries concerning estrogen receptors, on estrogen as a morphogen, and on the molecular mechanisms of anti-estrogen signaling.
Journal ArticleDOI
ESR1 mutations—a mechanism for acquired endocrine resistance in breast cancer
TL;DR: Preclinical and clinical development of rationale-based novel therapeutic strategies that inhibit these ER mutants has the potential to substantially improve treatment outcomes and evaluate how mutated ER can be detected and targeted to overcome resistance and improve patient outcomes.
Journal ArticleDOI
Pathways to tamoxifen resistance.
TL;DR: Common mechanisms of antiestrogen resistance are reviewed and the implications for prediction of response and design of effective combinatorial treatments are discussed.
Journal ArticleDOI
Resistance to chemotherapy: new treatments and novel insights into an old problem
S Raguz,Ernesto Yagüe +1 more
TL;DR: Recent findings with minimally transformed pretumorigenic primary human cells indicate that the ability to generate drug resistance arises early during the tumorigenic process, before the full transformation, raising the prospect of cell-targeted therapies instead of treatment directed against the whole tumour.
Journal ArticleDOI
The Role of the Epidermal Growth Factor Receptor in Breast Cancer
TL;DR: The role of EGFR in breast cancer is reviewed, and data from selected clinical trials of signal transduction inhibition of this cellular target are summarized.
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TL;DR: The 10-year and 15-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival are reported and it is found that the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis.
Journal ArticleDOI
Cloning of a novel receptor expressed in rat prostate and ovary.
TL;DR: It is concluded that clone 29 cDNA encodes a novel rat ER, which is suggested be named rat ERbeta to distinguish it from the previously cloned ER (ERalpha) from rat uterus.
Journal ArticleDOI
The Structural Basis of Estrogen Receptor/Coactivator Recognition and the Antagonism of This Interaction by Tamoxifen
Andrew K. Shiau,Danielle Barstad,Paula M. Loria,Lin Cheng,Peter J. Kushner,David A. Agard,Geoffrey L. Greene +6 more
TL;DR: Crystal structures of the human estrogen receptor alpha (hER alpha) ligand-binding domain (LBD) and the OHT-LBD complex reveal the two distinct mechanisms by which structural features of OHT promote this "autoinhibitory" helix 12 conformation.
Journal ArticleDOI
Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer
TL;DR: Anastrozole should be the preferred initial treatment for postmenopausal women with localised hormone-receptor-positive breast cancer, especially gynaecological problems and vascular events, but arthralgia and fractures were increased.
Journal ArticleDOI
Activation of the Estrogen Receptor Through Phosphorylation by Mitogen-Activated Protein Kinase
Shigeaki Kato,Hideki Endoh,Yoshikazu Masuhiro,Takuya Kitamoto,Shimami Uchiyama,Haruna Sasaki,Shoichi Masushige,Yukiko Gotoh,Eisuke Nishida,Hiroyuki Kawashima,Daniel Metzger,Pierre Chambon +11 more
TL;DR: The phosphorylation of the human estrogen receptor (ER) serine residue at position 118 is required for full activity of the ER activation function 1 (AF-1), which is modulated by the phosphorylated Ser118 through the Ras-MAPK cascade of the growth factor signaling pathways.
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