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The androgen receptor (AR) is expressed in many cell types, and its related signaling is widely investigated in hormone-dependent cancers such as prostate and breast. The significance of the AR, however, has been detected even in other cancers, including gastric, bladder, kidney, lung, hepatic, and pancreatic, in which growth and spreading are not strictly or notoriously dependent on sex steroid hormone action. The incidence and mortality of these cancers are, however, somewhat related to gender and, specifically, are higher in men than in women, with the ratio reaching 3–4:1 for bladder cancer. This direct correlation between cancer incidence, mortality, and gender makes sex one of the most important risk factors for these cancers and has incited investigation about the role of sex steroid receptors and their activating hormones in gender-related cancers. In these cancers, the AR is often expressed and seems to play a pivotal role in different processes contributing to cancer onset and progression such as growth, spreading, and epithelial to mesenchymal transition (EMT). This manuscript will offer an overview of the role of the AR in many cancers of the respiratory and gastrointestinal systems wherein its role has been at least partially analyzed. Understanding the role of the AR in these tumors could help us to identify a new biomarker for early diagnostic guidance and to develop better therapeutic approaches by directly targeting the AR or its downstream signaling in individual cells of hormone-related cancers at different stages.

Despite the improvements in diagnostic and therapeutic approaches, breast cancer still remains one of the world’s leading causes of death among women. Particularly, triple negative breast cancer (TNBC) is characterized by aggressiveness, metastatic spreading, drug resistance and a very high percentage of death in patients. Nowadays, identification of new targets in TNBC appears very compelling. TNBC are considered negative for the estrogen receptor alpha (ERα) expression. Nevertheless, they often express ERβ and its variants. As such, this TNBC subtype still responds to estrogens. While the ERβ1 variant seems to act as a tumor-suppressor, the two variants ERβ2 and 5 exhibit pro-oncogenic activities in TNBC. Thus, ERβ1 activation might be used to limit the growth and spreading as well as to increase the drug sensitivity of TNBC. In contrast, the pro-oncogenic properties of ERβ2 and ERβ5 suggest the possible development and clinical use of specific antagonists in TNBC treatment. Furthermore, the role of ERβ might be regarded in the context of the androgen receptor (AR) expression, which represents another key marker in TNBC. The relationship between AR and ERβ as well as the ability to modulate the receptor-mediated effects through agonists/antagonists represent a challenge to develop more appropriate therapies in clinical management of TNBC patients. In this review, we will discuss the most recent data in the field. Therapeutic implications of these findings are also presented in the light of the discovery of specific ERβ modulators.

Aging is accompanied by a progressive decrease in skeletal muscle mass and function. This process is characterized by the decrease of sex steroid hormone levels due to andropause and menopause. The axis androgens/androgen receptor (AR) sustains muscle size through classic (also called genomic) and non-classic (or non-genomic) actions to elicit various biological responses. Non-genomic androgen effects act through the crosstalk of AR with other partners. Recently, a specific interaction has been shown to occur through AR and filamin A or Src in different types of normal and malignant cells. From these interactions, the activation of several downstream effectors (paxillin, FAK, MAPK, Akt) follows. Such events induce cell proliferation and survival as well as metabolic changes. Irrespective of the sex of the individual, the more important signaling hubs linking the AR non-genomic circuit with cytoskeleton organization have been analyzed by the Western blot of lysate proteins from human skeletal muscle biopsies (obtained from both young and old patients) and C2C12 skeletal muscle cells. The phosphorylation of filamin A and paxillin increases in biopsies derived from old patients (>61 years), as compared with those derived from young patients (