Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer.

Androgen deprivation therapies (ADTs) are important treatments which inhibit androgen-induced prostate cancer (PCa) progression by either preventing androgen biosynthesis (e.g. abiraterone) or by antagonizing androgen receptor (AR) function (e.g. bicalutamide, enzalutamide, darolutamide). A major limitation of current ADTs is they often remain effective for limited durations after which patients commonly progress to a lethal and incurable form of PCa, called castration-resistant prostate cancer (CRPC) where the AR continues to orchestrate pro-oncogenic signalling. Indeed, the increasing numbers of ADT-related treatment-emergent neuroendocrine-like prostate cancers (NePC), which lack AR and are thus insensitive to ADT, represents a major therapeutic challenge. There is therefore an urgent need to better understand the mechanisms of AR action in hormone dependent disease and the progression to CRPC, to enable the development of new approaches to prevent, reverse or delay ADT-resistance. Interestingly the AR regulates distinct transcriptional networks in hormone dependent and CRPC, and this appears to be related to the aberrant function of key AR-epigenetic coregulator enzymes including the lysine demethylase 1 (LSD1/KDM1A). In this review we summarize the current best status of anti-androgen clinical trials, the potential for novel combination therapies and we explore recent advances in the development of novel epigenetic targeted therapies that may be relevant to prevent or reverse disease progression in patients with advanced CRPC.

Impressions of sexual unfaithfulness and their accuracy show a degree of universality.

Forming accurate impressions of others' trustworthiness is a critical social skill, with faithfulness representing a key aspect of trust in sexual relationships. Interestingly, there is evidence for a small degree of accuracy in facial impressions of sexual unfaithfulness. Theoretical accounts suggest that these impressions may function to help with partner selection, and may be universal. If so, impressions should be similar for perceivers from different cultures and accuracy should not be limited to own-race faces. We tested these predictions by asking Caucasian and Asian women to judge the likelihood of unfaithfulness from the faces of Caucasian males whose past sexual history was known. In two studies we found high cross-cultural agreement in these impressions, consistent with universality in the impressions themselves. In Study 1, we found an other-race effect in impression accuracy, with significantly less accurate cross-race impressions by Asian women than own-race impressions by Caucasian women. Asian women showed no accuracy. Interestingly, in Study 2, Asian women who had grown up in the West showed small but significant accuracy in their impressions, with no other-race effect. Results are consistent with a degree of universality in the accuracy of this important aspect of social perception, provided that perceivers have experience with the faces being assessed.