Substantial advances have been made in the development of therapeutic biomarkers in various cancers, but not in prostate cancer. A germline inherited polymorphic variant (1245A→C) in the HSD3B1 gene was recently reported to correlate with shorter duration of response to androgen-deprivation therapy (ADT) in hormone-sensitive prostate cancer (HSPC).1 The HSD3B1 gene encodes the enzyme 3β-hydroxysteroid dehydrogenase-1 (3βHSD1), which catalyzes adrenal androgen precursors into dihydrotestosterone, the most potent androgen.2,3 In the study by Hearn et al,1 presence of 1 or more variant alleles of the HSD3B1 (1245C) was associated with decreased progression-free survival (PFS) compared with the absence of any variant alleles in 3 cohorts of men with prostate cancer treated with ADT: 2 cohorts with post-prostatectomy biochemical recurrence, and 1 cohort with metastatic HSPC (mHSPC) (total, n = 443). In the present analysis, we provide, to our knowledge, the first independent validation of these results, which have the potential to introduce the first predictive biomarker of response to therapy for this patient population.
Agarwal N, Hahn AW, Gill DM, Farnham JM, Poole AI, Cannon-Albright L. Independent Validation of Effect of HSD3B1 Genotype on Response to Androgen-Deprivation Therapy in Prostate Cancer. JAMA Oncol. Published online February 16, 2017. doi:10.1001/jamaoncol.2017.0147