The Androgen Receptor (AR) is emerging as an important factor in the pathogenesis of breast cancer (BC), which is the most common malignancy among females worldwide. The concordance of more than 70% of AR expression in primary and metastatic breast tumors implies that AR may be a new marker and a potential therapeutic target among AR-positive breast cancer patients. Biological insight into AR-positive breast cancer reveals that AR may cross-talk with several vital signaling pathways, including key molecules and receptors. AR exhibits different behavior depending on the breast cancer subtype. Preliminary clinical research using AR-targeted drugs, which have already been FDA-approved for prostate cancer (PC), has given promising results for AR-positive breast cancer patients. However, since the prognostic and predictive value of AR positivity remains uncertain, it is difficult to identify and stratify patients that would benefit from AR-targeted therapies. Herein, through a review of preclinical studies, clinical studies, and clinical trials, we summarize the biology of AR, its prognostic and predictive value, as well as its therapeutic implications by breast cancer molecular subtype.

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Despite the advances in systemic chemotherapy, gastric adenocarcinoma (GC) remains the third most common cause of cancer-related deaths with poor prognosis. The heterogeneity of GC indicates that novel biomarkers should be established in order to further classify tumors and develop individual targeted therapies. High-quality preclinical and clinical research has demonstrated that growth factor (HGF)-hepatocyte growth factor receptor (c-Met) pathway plays a pivotal role on the growth, survival and invasiveness of GC. In particular, aberrant activation of HGF/c-Met signaling pathway has been associated with poor clinical outcomes, suggesting the therapeutic potential of c-Met. This has stimulated the development and evaluation of a number of c-Met targeted agents in an advance disease setting. In this review, we summarize the current state of the art in the advances on the inhibition of c-Met pathway, with particular emphasis on the clinical testing of c-Met targeted therapeutic agents. Furthermore, we discuss the challenges facing the incorporation of c-Met targeted agents in randomized trials, with the idea that the definition of the appropriate genetic and molecular context for the use of these agents remains the priority.

Objective-Although animal studies indicate that liver X receptor alpha (LXR␣) might influence risk of atherosclerosis, data in humans remain scarce. We tested the hypothesis that genetic variation in LXR␣ associates with risk of ischemic vascular disease and/or plasma lipid and lipoprotein levels in the general population. Methods and Results-We studied 10,281 white persons of Danish ancestry from a general population cohort, including 1,986 in whom ischemic heart disease (IHD) developed, and 989 in whom ischemic cerebrovascular disease developed. We examined another 51,429 white persons of Danish ancestry from a general population study, including 3,789 with IHD. We genotyped 10 genetic variants identified by resequencing LXR␣. Homozygosity for Ϫ840AA/ Ϫ115AA(ϭ2.7%) predicted hazard ratios of 1.3 (95% confidence interval, 1.0 -1.7) for IHD, 1.6 (1.2-2.2) for myocardial infarction, and 1.7 (1.3-2.4) for ischemic cerebrovascular disease. The corresponding odds ratios in the second cohort were 1.1 (0.9 -1.4) for IHD and 1.5 (1.1-2.0) for myocardial infarction. In the combined studies, odds ratios were 1.2 (1.0 -1.4) for IHD and 1.5 (1.2-1.9) for myocardial infarction. Homozygosity for Ϫ840AA/Ϫ115AA did not associate with lipid or lipoprotein levels. LXR␣ Ϫ1830TϾC (tagging the haplotype Ϫ1830C/Ϫ840A/Ϫ115A, all r 2 Ն0.97) associated with 91% increased transcriptional activity. Key Words: coronary heart disease Ⅲ epidemiology Ⅲ gene mutations Ⅲ ischemic heart disease Ⅲ stroke L iver X receptor alpha (LXR␣) is a nuclear receptor that plays a central role in both lipid metabolism and inflammation. 1 LXR␣ is activated by increased intracellular levels of oxysterols, a breakdown product of cholesterol, and orchestrates the removal of cholesterol from peripheral tissues by regulating genes involved in reverse cholesterol transport. 2 Other downstream effects of LXR␣ activation include increases in catabolism, biliary excretion, and conversion to fatty acids of cholesterol. 3 Furthermore, LXR␣ modulates the immune response via an antiinflammatory effect on macrophages. 4 Because plasma cholesterol levels as well as inflammatory processes are key players in the development of the atherosclerotic plaque, a possible role of LXR␣ in ischemic cardiovascular and ischemic cerebrovascular disease (ICVD) has been the focus of intense research. 1 Several studies have demonstrated that LXR␣ agonists attenuate the development of atherosclerosis in mice and protect against neuronal damage in animal models of ischemic stroke (IS). 5,6 Further underpinning a possible role of LXR␣ in ischemic vascular disease is the observation that LXR␣ knockout mice display an increased susceptibility to atherosclerosis and IS. 6,7 However, data pertaining to LXR␣ biology in humans remain scarce. Conclusion-This study suggests that functional genetic variation inWe hypothesized that genetic variation in LXR␣ might influence risk of ischemic vascular disease and/or plasma lipid and lipoprotein levels in the general population. To test this hypothesis, w...