Advances in the understanding of androgen receptor structure and function and in the development of next-generation AR-targeted therapeutics.

[Display omitted] • The incidence of prostate cancer is 50% higher and mortality is two times higher in American black men than in American white men. • AR has the propensity to form phase separated droplets that can help overcome antiandrogen resistance. • AR is implicated for the sexual dimorphism in response to BRAF/MEK inhibitors for melanoma. • Gain of function in the Androgen receptor results in the neuromuscular disease, spinal bulbar and muscular atrophy (SBMA). • Drugs targeting the AR range from LBD-binding antagonist, NTD-binding antagonist, and PROTACS. Androgen receptor (AR) and its ligand androgens are important for development and physiology of various tissues. AR and its ligands also play critical role in the development of various diseases, making it a valuable therapeutic target. AR ligands, both agonists and antagonists, are being widely used to treat pathological conditions, including prostate cancer and hypogonadism. Despite AR being studied widely over the last five decades, the last decade has seen striking advances in the knowledge on AR and discoveries that have the potential to translate to the clinic. This review provides an overview of the advances in AR biology, AR molecular mechanisms of action, and next generation molecules that are currently in development. Several of the areas described in the review are just unraveling and the next decade will bring more clarity on these developments that will put AR at the forefront of both basic biology and drug development. [ABSTRACT FROM AUTHOR]