Abstract

Among different types of breast cancers (BC), triple-negative BC (TNBC) amounts to 15-20 percent of breast malignancies. Three principal characteristics of TNBC cells are 1) extreme aggressiveness, 2) absence of hormones, and 3) growth factor receptors. Due to the lack or poor expression of estrogen-receptor (ER), human epidermal growth factor receptor 2 (HER2), and progesterone-receptor (PR), TNBC is resistant to hormones and endocrine therapies. Consequently, chemotherapy is currently utilized as the primary approach against TNBC. Expression of androgen receptor (AR) in carcinoma cells has been observed in a subset of patients with TNBC; therefore, inhibiting androgen signaling pathways holds promise for TNBC targeting. The new AR inhibitors have opened up new therapy possibilities for BC patients carrying AR-positive TNBC cells. Our group provides a comprehensive review of the structure and function of the AR and clinical evidence for targeting the cell's nuclear receptor in TNBC. We updated AR agonists, inhibitors, and antagonists. We also presented a new era of genetic manipulating CRISPR/Cas9 and nanotechnology as state of the art approaches against AR to promote the efficiency of targeted therapy in TNBC.

Significance Statement The lack of effective treatment for TNBC is a health challenge. The main disadvantages of existing treatments are their side effects, due to their non-specific targeting. Molecular targeting of cellular receptors, such as AR, increased expression in malignant tissues significantly improving the survival rate of breast cancer patients.