Newly Developed Targeted Therapies Against the Androgen Receptor in Triple-Negative Breast Cancer: A Review

Among different types of breast cancers (BC), triple-negative BC (TNBC) amounts to 15% to 20% of breast malignancies. Three principal character-istics of TNBC cells are (i) extreme aggressiveness, (ii) absence of hormones, and (iii) growth factor receptors. Due to the lack or poor expression of the es-trogen receptor, human epidermal growth factor re-ceptor 2, and progesterone receptor, TNBC is resistant to hormones and endocrine therapies. Consequently, chemotherapy is currently used as the primary approach against TNBC. Expression of androgen recep-tor (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 pos-sibilities 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 up-dated 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 ther-apy in TNBC.Significance Statement--The lack of effective treat-ment for triple-negative breast cancer is a health challenge. The main disadvantages of existing treatments are their side effects, due to their nonspecific targeting. Molecular targeting of cellular receptors, such as androgen receptors, increased expression in malignant tissues, significantly im-proving the survival rate of breast cancer patients.