As accumulating evidence has shown that long non-coding RNAs (lncRNAs) regulate important cancer hallmarks, we hypothesised that AR-regulated lncRNAs might play roles in TNBC progression.
There is increasing evidence that Androgen Receptor (AR) expression has prognostic usefulness in Triple negative breast cancer (TNBC), where tumors that lack AR expression are considered "Quadruple negative" Breast Cancers ("QNBC").
By examining the expression of AR in patients with TNBC, the aim of the present study is to explore the clinical significance of AR and provide evidence for AR-directed treatment in TNBC.
In the present review, potentially carcinogenic signaling pathways in TNBCs from previous reports were considered, and ultimately five tumorigenic signaling pathways were selected, specifically receptor tyrosine kinases and downstream signaling pathways, the epithelial-to-mesenchymal transition and associated pathways, the immunoregulatory tumor microenvironment, DNA damage repair pathways, and AR and coordinating pathways.
HER2<sup>+</sup> and triple-negative breast cancer cell lines were treated with AR antagonist plus anti-HER2 mAb trastuzumab or mTOR inhibitor everolimus.
Additionally, combination of enzalutamide with BMS-754807 or NVP-AEW541 exerted significant reductions in TNBC proliferation even in cells with low AR expression (<i>p</i> < 0.001).
We also review the aberrant activated signals found in different subgroups of TNBC, including androgen receptor (AR) and PI3K/AKT/mTOR, Notch, Wnt/β-catenin, Hedge-hog, and TGF-β signaling pathways, which play essential roles in multiple development stages of TNBC.
Several molecular targets are being explored to target TNBC including androgen receptor, epidermal growth factor receptor (EGFR), poly(ADP-ribose) polymerase (PARP), and vascular endothelial growth factor (VEGF).
Tumoral heterogeneity and the presence of several subtypes of TNBC such as Basal like (BL)-1, BL-2, immune-modulatory, luminal androgen receptor, mesenchymal, and mesenchymal/stem like subtype and claudin low subtype, may explain some of the difficulties faced in managing this challenging disease subgroups.
Our study has indicated that the absence of AR might help to identify patients with relatively higher risk of disease relapse and death, and further clinical studies of anti-androgen agents are warranted to enrich the therapeutic strategy options for AR+ TNBCs.
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.
However, the role of ERβ1 in the metastasis of androgen receptor (AR)-positive triple-negative breast cancer (TNBC) and the underlying mechanisms are still unknown.
In this retrospective study we evaluated the prognostic role of 4 different molecular determinants, including androgen receptor (AR), E-cadherin (CDH1), Ki67 index, and basal cytokeratins (CKs) 5/6, in a cohort of 99 patients with TNBC.
The combinations of high proliferation, metaplastic features, and immunohistochemical statuses of some EMT and basal-like markers and androgen receptor appeared to be able to characterize the TNBCs that showed cPD after NAC.
In triple-negative breast cancer, miRNA expressions are found to be associated with BRCA mutations, immune system, epithelial-mesenchymal transition, cancer stem cell properties and androgen receptor expression.
We demonstrated that combination of AR antagonist (bicalutamide) and PARP inhibitor (ABT-888) could inhibit cell viability and induce cell apoptosis significantly whatever in vitro or in vivo setting in AR-positive TNBC.
Numerous experimental approaches are under way, and several encouraging drug classes, such as immune checkpoint inhibitors, poly(ADP-ribose) polymerase inhibitors, platinum agents, phosphatidylinositol-3-kinase pathway inhibitors, and androgen receptor inhibitors, are being investigated in TNBC.