Multiple Molecular Subtypes of Triple-Negative Breast Cancer Critically Rely on Androgen Receptor and Respond to Enzalutamide In Vivo

@article{Barton2015MultipleMS,
  title={Multiple Molecular Subtypes of Triple-Negative Breast Cancer Critically Rely on Androgen Receptor and Respond to Enzalutamide In Vivo},
  author={Valerie N. Barton and Nicholas C. D’Amato and Michael A Gordon and Hanne Lind and Nicole S. Spoelstra and Beatrice L Babbs and Richard E Heinz and Anthony D Elias and Paul Jedlicka and Britta M. Jacobsen and Jennifer K. Richer},
  journal={Molecular Cancer Therapeutics},
  year={2015},
  volume={14},
  pages={769 - 778}
}
Triple-negative breast cancer (TNBC) has the lowest 5-year survival rate of invasive breast carcinomas, and currently there are no approved targeted therapies for this aggressive form of the disease. [...] Key Result Indeed, AR inhibition significantly reduces baseline proliferation, anchorage-independent growth, migration, and invasion and increases apoptosis in four TNBC lines (SUM159PT, HCC1806, BT549, and MDA-MB-231), representing three non-LAR TNBC molecular subtypes (mesenchymal-like, mesenchymal stem…Expand
TITLE: Targeting Androgen Receptor in Breast Cancer: Enzalutamide as a Novel Breast Cancer Therapeutic PRINCIPAL INVESTIGATOR:
Triple-negative breast cancer (TNBC) has the lowest 5-year survival rate of invasive breast carcinomas, and currently there are no approved targeted therapies for this aggressive form of the disease.Expand
Role of the androgen receptor in triple-negative breast cancer.
TLDR
Despite lower pathologic complete response (pCR) rates with neoadjuvant therapy, patients with AR-dependent TNBCs have a better prognosis than those with T NBCs that are not AR- dependent, and this paper describes the results of early clinical trials with antiandrogens in this population. Expand
Preclinical evaluation of the AR inhibitor enzalutamide in triple-negative breast cancer cells.
TLDR
Targeting of the AR with drugs such as enzalutamide may provide an alternative treatment strategy for patients with AR-positive TNBC, and appears to mediate these processes through down-regulation of the transcription factors AP-1 and SP-1. Expand
Androgen receptor in triple negative breast cancer: A potential target for the targetless subtype.
TLDR
Clinical evidence suggests a role for anti-androgen therapies such as bicalutamide, enzalutamide and abiraterone, offering an interesting chemo-free alternative for chemo -unresponsive patients, and therefore potentially shifting current treatment strategies. Expand
The role of the androgen receptor in triple-negative breast cancer
TLDR
AR-targeted therapy is one of the envisioned new therapies for TNBC; the therapeutic approach can involve the inhibition of androgen synthesis, use of non-androgenic AR-binding hormones, inhibition of co-regulators, activation of membrane AR, and reassessment of medroxyprogesterone acetate. Expand
Targeting the androgen receptor in triple-negative breast cancer: current perspectives
TLDR
As novel AR-targeting agents are developed and evaluated in clinical trials, it is equally important to establish a robust set of biomarkers for identification of TNBC tumors that are most likely to respond to AR inhibition. Expand
Response to mTOR and PI3K inhibitors in enzalutamide-resistant luminal androgen receptor triple-negative breast cancer patient-derived xenografts
TLDR
It is found that mTOR and PI3K inhibitors had marked antitumor activity in vivo in PDX harboring genomic alterations of PIK3CA and AKT1 genes that did not respond to the AR antagonist enzalutamide. Expand
Functional characterization of androgen receptor in two patient-derived xenograft models of triple negative breast cancer
TLDR
The results do not support that AR is a suitable therapeutic target in TNBC, and suggest that TN1 and TN2, which both express functional AR, are two molecularly distinct PDX models. Expand
Antiproliferative Effect of Androgen Receptor Inhibition in Mesenchymal Stem-Like Triple-Negative Breast Cancer
TLDR
This study demonstrates the tumorigenesis role of AR and the inhibitory effect of bicalutamide in AR- positive MSL TNBC both in vitro and in vivo, suggesting that AR inhibition could be a potential therapeutic approach for AR-positive TNBC patients. Expand
Anti-androgen therapy in triple-negative breast cancer
TLDR
The drug development pipeline of AR-targeted therapeutics in prostate cancer is facilitating the evaluation of AR signaling inhibition in triple-negative breast cancer (TNBC), and preclinical modeling suggests that its functional role in disease progression is subtype-specific. Expand
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