2017
DOI: 10.1101/214155
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Overcoming Resistance to Anabolic Selective Androgen Receptor Modulator (SARM) Therapy in Experimental Cancer Cachexia with Histone Deacetylase Inhibitor AR-42

Abstract: BackgroundCancer cachexia impacts the majority of advanced cancer patients but no approved anticachexia therapeutic exits. Recent late stage clinical failures of anabolic anti-cachexia therapy revealed heterogeneous responses to anabolic therapies and a limited ability to translate improved body composition into functional benefit. It is currently unclear what governs anabolic responsiveness in cachectic patient populations. Methods We evaluated anabolic androgen therapy combined with the novel anti-cachectic … Show more

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Cited by 2 publications
(2 citation statements)
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References 105 publications
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“…For example, there are reports that the histone deacetylase (HDAC) inhibitor, AR-42, is a potent inhibitor of STAT3 activity [49]. Recent experiments in the C26 cachexia mouse model using anabolic androgen therapy in combination with HDAC inhibitor AR-42 was shown to block STAT3 mediated muscle atrophy [163]. Ruxolitinib, a Jak1/2 inhibitor has also been found to result in a significant increase in body weight, in a phase II trial, in exocrinemetastatic pancreatic cancer patients [50,51].…”
Section: Stat3 and Cachexiamentioning
confidence: 99%
“…For example, there are reports that the histone deacetylase (HDAC) inhibitor, AR-42, is a potent inhibitor of STAT3 activity [49]. Recent experiments in the C26 cachexia mouse model using anabolic androgen therapy in combination with HDAC inhibitor AR-42 was shown to block STAT3 mediated muscle atrophy [163]. Ruxolitinib, a Jak1/2 inhibitor has also been found to result in a significant increase in body weight, in a phase II trial, in exocrinemetastatic pancreatic cancer patients [50,51].…”
Section: Stat3 and Cachexiamentioning
confidence: 99%
“…In the anti-proliferation assay against LNCaP cells, compound 68 shows greater activity than apalutamide (ARN-509) [209]. The dual AR-HDACs inhibitor might have potential treatment benefit for anti-cachectic therapy [210] or castration-resistant prostate cancer [211]. <insert Table 19>…”
Section: Dual Inhibitors Of Hdacs and Nuclear Receptors 241 Dual Inhi...mentioning
confidence: 99%