Drug discovery today
-
Drug discovery today · Sep 2014
ReviewStrategies for targeting the androgen receptor axis in prostate cancer.
Androgen receptor (AR) signaling plays a critical role in prostate cancer cell proliferation, survival, and differentiation. Therapeutic strategies targeting the androgen receptor have been developed for the treatment of metastatic hormone-naïve prostate cancer; however, despite effective targeting recent studies have demonstrated that during progression to a castrate-resistant phenotype there is restoration of AR target gene expression. On the basis of this observation, second-generation therapeutics have been developed to target AR in the castrate-resistant setting resulting in a survival benefit. In this review we will discuss the mechanisms promoting AR signaling and the development of second-generation therapeutics targeting AR in castrate-resistant prostate cancer.
-
Drug discovery today · Sep 2014
Review Comparative StudyReversal of target-specific oral anticoagulants.
Target-specific oral anticoagulants (TSOACs) provide safe and effective anticoagulation for the prevention and treatment of thrombosis in a variety of clinical settings by interfering with the activity of thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban, edoxaban, betrixaban). Although TSOACs have practical advantages over vitamin K antagonists (VKAs), there are currently no antidotes to reverse their anticoagulant effect. ⋯ We discuss important limitations of existing evidence, which is derived from studies in human volunteers, animal models and in vitro experiments. Studies evaluating the safety and efficacy of reversal agents on clinical outcomes such as bleeding and mortality in patients with TSOAC-associated bleeding are needed.