MDM2 and neoplasm: Potential mechanisms of AR activation despite lack of androgens include mutations of the AR receptor itself, posttranslational modification of the AR receptor, mutations in transcriptional co‐regulators (eg, NCOA and NCOR co‐regulator groups), androgen synthesis within the tumor, activation of AR modulatory kinase pathways resulting in hormone dependent but androgen independent activity (eg, via PI3K activation) and altered AR degradation (eg, by E3 ubiquitin ligases Mdm2 activity.