Selective Androgen Receptor Modulator RAD140 Inhibits the Growth of Androgen/Estrogen Receptor–Positive Breast Cancer Models with a Distinct Mechanism of Action

@article{Yu2017SelectiveAR,
  title={Selective Androgen Receptor Modulator RAD140 Inhibits the Growth of Androgen/Estrogen Receptor–Positive Breast Cancer Models with a Distinct Mechanism of Action},
  author={Ziyang Yu and Suqin He and Dannie Wang and Hitisha K. Patel and Chris P. Miller and Jeffrey L. Brown and G. Hattersley and Jamal C. Saeh},
  journal={Clinical Cancer Research},
  year={2017},
  volume={23},
  pages={7608 - 7620}
}
Purpose: Steroidal androgens suppress androgen receptor and estrogen receptor positive (AR/ER+) breast cancer cells and were used to treat breast cancer, eliciting favorable response. The current study evaluates the activity and efficacy of the oral selective AR modulator RAD140 in in vivo and in vitro models of AR/ER+ breast cancer. Experimental Design: A series of in vitro assays were used to determine the affinity of RAD140 to 4 nuclear receptors and evaluate its tissue-selective AR activity… 
The cellular and molecular effects of the androgen receptor agonist , Cl-4 AS-1 , on breast cancer cells
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The cellular and molecular effects of the androgen receptor agonist, Cl-4AS-1, on breast cancer cells
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RAD140 is a novel oral AR-targeted agent for the treatment of AR+/ER+/HER2- mBC with an acceptable safety profile and preliminary evidence of target engagement and antitumor activity.
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This review aims to elucidate whether androgens might influence the susceptibility for breast cancer, and the possibility to exploit the AR as a useful marker to predict the disease will be also evaluated.
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Preclinical insights into the role of Type 1 NRs in breast cancer that have served as a catalyst for clinical translation are reviewed and the potential to translate these findings into improving patient outcomes is discussed.
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TLDR
An optimal AR cut-point is defined to reliably predict breast cancer survival and testing this cut- point in prospective cohorts is warranted for implementation of AR as a prognostic factor in the clinical management of breast cancer.
Estrogen Receptor on the move: Cistromic plasticity and its implications in breast cancer.
TLDR
The current state-of-the-art on which factors manipulate the ERα cistrome is described and how this alters the response to both endogenous and exogenous hormonal stimuli, ultimately impacting BCa cell progression and response to commonly used therapeutic interventions.
Comparison of the three SARMs RAD-140, GLPG0492 and GSK-2881078 in two different in vitro bioassays, and in an in silico androgen receptor binding assay
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Androgenic activity of the three non-steroidal compounds in the two different in vitro test systems confirmed the results of the in silico modeling of the androgen receptor binding.
Androgen receptor expression and steroid action in bone
TLDR
This review summarizes the current knowledge of the gain-of-function and loss- of-function attributes of these two steroid hormones with specific emphasis on androgens and male skeletal health.
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