Nima Sharifi: HSD3B1 and outcomes with ADT+enzalutamide in ARCHES
Nima Sharifi, shared a post on X:
“1. Very glad that our story on HSD3B1 and clinical outcomes with ADT+enzalutamide in ARCHES is finally out in Cell Reports Medicine with Andrew Armstrong, Arun Azad, Arnulf Stenzl, Desai Sethi Urology Institute, Sylvester Comprehensive Cancer Center, and PCF Science.
2. What did we know before this study, Men with adrenal-permissive (hyperactive) HSD3B1 enzyme and low volume (LV) metastatic prostate cancer progress more quickly and have shorter survival when hormonal therapy is ADT (or castration) alone – from E3805.
3. Why is that, The missense encoded by the adrenal-permissive HSD3B1 allele allows tumors to use non-gonadal androgens for tumor progression. Effect seen in LV disease doesn’t appear to occur in HV disease, probably b/c HV tumors are more complex.
4. So what happens in LV disease in ARCHES w/ ADT +/- enz, Does that reverse poor outcomes with the adrenal-permissive allele, Too early to tell for ADT+enz (see below). You can see HSD3B1 curves visually separating for ADT alone (similar to E3805) but no sig. difference here.
5. Events in this ARCHES analysis are driven by outcomes in HV disease and thus no sig. difference by HSD3B1 genotype. However, there may be some difference in adverse effects. Why would that be, Perhaps estrogens, as enzyme encoded by HSD3B1 is also 1 step upstream of aromatase.
6. I’m grateful to all my co-authors, especially Andrew Armstrong and Duke Cancer. Also, this isn’t the end of the story, Stay tuned for more to come soon on HSD3B1 in LV metastatic prostate cancer.”
HSD3B1 Genotype and Clinical Outcomes in Metastatic Castration-Sensitive Prostate Cancer
Authors: Jason W. D. Hearn, Christopher J. Sweeney, Nima Almassi et al
Source: Nima Sharifi/X