HSD3B1 and me.

Ever at a cookout and think to yourself, “hamburger or hotdog?” We usually go with both. After CHAARTED, STAMPEDE, and LATITUDE, we’re kinda in the same position for bad-acting prostate cancer (minus the indigestion). Docetaxel or total androgen ablation? A possible answer to this question is slowly evolving with two new studies that explore the utility of HSD3B1 gene variants in the settings of biochemical recurrence (BR) and castrate-resistance. HSD3B1 encodes the protein 3-beta-HSD1, which produces the potent androgen DHT (cue guitar riff). Some men have one or both HSD3B1 allele variants, making this protein resistant to degradation. We already know this is bad news when it comes to responses to first-line ADT. But, interestingly, this variant allele was associated with better outcomes with nonsteroidal androgen deprivation (e.g., with ketoconazole). Huh? The thought is that the variant HSD3B1 may drive extra-gonadal androgen synthesis leading to a castrate-resistance responsive to extra-gondal androgen suppression...and the rest we’ll leave to docetaxel. Ok, is it time for dessert yet?