Selective androgen receptor modulators for the prevention and treatment of muscle wasting associated with cancer

Dalton, James T.; Taylor, R. A. J.; Mohler, Michael L.; Steiner, Mitchell S.

doi:10.1097/spc.0000000000000015

Cited by 77 publications

(46 citation statements)

References 33 publications

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“…The important role played by androgens in regulation of muscle mass and aetiology of prostate cancer has led to development of compounds that are classified as SARMs and are designed to maintain well-being in men without causing prostatic hyperplasia or malignancy. A recent review highlighted positive impacts of SARMs on cancer-associated muscle wasting (Dalton et al 2013). Although limited evidence has been presented to date, press reports on one SARM (Enobosarm, Gtx, Inc., Memphis, TN, USA) highlight preliminary (unpublished) data of a trial testing use as a therapy for women with metastatic breast cancer (http://phx.corporate-ir.…”

Section: Future Perspectivesmentioning

confidence: 99%

Evidence of androgen action in endometrial and ovarian cancers

Gibson

Simitsidellis

Collins

et al. 2014

Endocrine-Related Cancer

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Endometrial cancer (EC) and ovarian cancer are common gynaecological malignancies. The impact of androgen action in these cancers is poorly understood; however, there is emerging evidence to suggest that targeting androgen signalling may be of therapeutic benefit. Epidemiological evidence suggests that there is an increased risk of EC associated with exposure to elevated levels of androgens, and genetic variants in genes related to both androgen biosynthesis and action are associated with an increased risk of both EC and ovarian cancer. Androgen receptors (ARs) may be a potential therapeutic target in EC due to reported anti-proliferative activities of androgens. By contrast, androgens may promote growth of some ovarian cancers and anti-androgen therapy has been proposed. Introduction of new therapies targeting ARs expressed in EC or ovarian cancer will require a much greater understanding of the impacts of cell context-specific AR-dependent signalling and how ARs can crosstalk with other steroid receptors during progression of disease. This review considers the evidence that androgens may be important in the aetiology of EC and ovarian cancer with discussion of evidence for androgen action in normal and malignant endometrial and ovarian tissue.

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Section: Future Perspectivesmentioning

confidence: 99%

Evidence of androgen action in endometrial and ovarian cancers

Gibson

Simitsidellis

Collins

et al. 2014

Endocrine-Related Cancer

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“…Therefore, androgenicanabolic steroids abuse-induced side effects on various systems and organs are addressed, including cardiovascular effects, central nervous system, male and female reproductive system, etc (Bassil et al 2009). Therefore, the development of tissue selective androgens, or selective AR modulators (SARMs) to achieve anabolic effects on such tissue as skeletal muscle without androgenic actions such as effects on prostate is of great clinical interest (Clarke and Khosla 2010;Dalton et al 2013). An alternative method to increase the endocrine secretion of endogenous androgens is to stimulate the endocrine system to release various hormones that in turn mimic, boost or result in the release of higher serum androgen levels.…”

mentioning

confidence: 99%

Effects of Tribulus terrestris saponins on exercise performance in overtraining rats and the underlying mechanisms

Yin

Wang

et al. 2016

Can. J. Physiol. Pharmacol.

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The objective of this study was to determine the effects of Tribulus terrestris L. (TT) saponins on exercise performance and the underlying mechanisms. A rat overtraining model was established and animals were treated with TT extracts (120 mg/kg body mass) 30 min before each training session. Serum levels of testosterone and corticosterone and levels of androgen receptor (AR) and insulin growth factor-1 receptor (IGF-1R) in the liver, gastrocnemius, and soleus were determined by ELISA and Western blot. Treatment of rats with TT saponins significantly improved the performance of the overtraining rats, reflected by the extension of time to exhaustion, with a concomitant increase in body mass, relative mass, and protein levels of gastrocnemius. Overtraining alone induced a significant decrease in the serum level of testosterone. In contrast, treatment with TT saponins dramatically increased the serum level of testosterone in overtraining rats to about 150% of control and 216% of overtraining groups, respectively. In addition, TT saponins resulted in a further significant increase in AR in gastrocnemius and significantly suppressed the overtraining-induced increase in IGF-1R in the liver. These results indicated that TT saponins increased performance, body mass, and gastrocnemius mass of rats undergoing overtraining, which might be attributed to the changes in androgen-AR axis and IGF-1R signaling.

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“…The benzene ring of the anilide has a trifluoromethyl group in meta-position and a nitro-or cyano-group in para-position. The chemical scaffold of Bic has been studied well by means of structure-activity relationships (Kirkovsky et al 2000, Bohl et al 2005b) and has also served as a template for the development of several selective AR modulators (SARMs), such as Ostarine and LGD-4033 (Dalton et al 2013). The structures of RD162, MDV3100 (enz), and ARN-509 are based on that of RU59063, a non-steroidal arylthiohydantoin AR agonist that binds AR with the highest known affinity (in the nanomolar range) (Jung et al 2010).…”

Section: Mechanism Of Action Of Antiandrogensmentioning

confidence: 99%

Androgen receptor antagonists for prostate cancer therapy

Helsen¹,

Broeck²,

Voet³

et al. 2014

Endocrine-Related Cancer

123

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Androgen deprivation is the mainstay therapy for metastatic prostate cancer (PCa). Another way of suppressing androgen receptor (AR) signaling is via AR antagonists or antiandrogens. Despite being frequently prescribed in clinical practice, there is conflicting evidence concerning the role of AR antagonists in the management of PCa. In the castration-resistant settings of PCa, docetaxel has been the only treatment option for decades. With recent evidence that castration-resistant PCa is far from AR-independent, there has been an increasing interest in developing new AR antagonists. This review gives a concise overview of the clinically available antiandrogens and the experimental AR antagonists that tackle androgen action with a different approach.

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Selective androgen receptor modulators for the prevention and treatment of muscle wasting associated with cancer

Cited by 77 publications

References 33 publications

Evidence of androgen action in endometrial and ovarian cancers

Evidence of androgen action in endometrial and ovarian cancers

Effects of Tribulus terrestris saponins on exercise performance in overtraining rats and the underlying mechanisms

Androgen receptor antagonists for prostate cancer therapy

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