biostudies-literatureGraham LSNCI NIH HHSProstate Cancer FoundationJanssen Pharmaceuticals418-426https://www.ebi.ac.uk/biostudies/studies/S-EPMC8044035biostudies-literatureUnknown81(7)<h4>Background</h4>Localized prostate cancers (PCs) may resist neoadjuvant androgen receptor (AR)-targeted therapies as a result of persistent intraprostatic androgens arising through upregulation of steroidogenic enzymes. Therefore, we sought to evaluate clinical effects of neoadjuvant indomethacin (Indo), which inhibits the steroidogenic enzyme AKR1C3, in addition to combinatorial anti-androgen blockade, in men with high-risk PC undergoing radical prostatectomy (RP).<h4>Methods</h4>This was an open label, single-site, Phase II neoadjuvant trial in men with high to very-high-risk PC, as defined by NCCN criteria. Patients received 12 weeks of apalutamide (Apa), abiraterone acetate plus prednisone (AAP), degarelix, and Indo followed by RP. Primary objective was to determine the pathologic cThe ProstateTargeting backdoor androgen synthesis through AKR1C3 inhibition: A presurgical hormonal ablative neoadjuvant trial in high-risk localized prostate cancer.PMC8044035T32 CA009515P01 CA163227P30 CA015704W81XWH‐18‐PC180686R50 CA221836P50 CA097186Schade GRYu EYSchweizer MTNega KHou WMLin DWGrivas PMontgomery BMatsumoto AAAlexander KGulati RMarck BSharifi NMostaghel EAGraham LSYezefski TTrue LDReder NPWright JNelson PSEllis WJfalseTargeting backdoor androgen synthesis through AKR1C3 inhibition: A presurgical hormonal ablative neoadjuvant trial in high-risk localized prostate cancer.<h4>Background</h4>Localized prostate cancers (PCs) may resist neoadjuvant androgen receptor (AR)-targeted therapies as a result of persistent intraprostatic androgens arising through upregulation of steroidogenic enzymes. Therefore, we sought to evaluate clinical effects of neoadjuvant indomethacin (Indo), which inhibits the steroidogenic enzyme AKR1C3, in addition to combinatorial anti-androgen blockade, in men with high-risk PC undergoing radical prostatectomy (RP).<h4>Methods</h4>This was an open label, single-site, Phase II neoadjuvant trial in men with high to very-high-risk PC, as defined by NCCN criteria. Patients received 12 weeks of apalutamide (Apa), abiraterone acetate plus prednisone (AAP), degarelix, and Indo followed by RP. Primary objective was to determine the pathologic c2021-01-01T00:00:00Z2021 May2026-05-30T22:54:16.511Z2024-11-21T02:18:34.067ZS-EPMC80440353375522510.1002/pros.24118