24 Feb Genetic Mutation May Predict Outcomes of Prostate Cancer Treated With Androgen-Deprivation Therapy or Abiraterone
MedicalResearch.com Interview with:
Masaki Shiota MD, PhD
Department of Urology
Graduate School of Medical Sciences
Fukuoka , Japan
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: 3β-hydroxysteroid dehydrogenase-1 encoded by HSD3B1 is a rate-limiting enzyme required for all pathways of dihydrotestosterone synthesis, as well as converts abiraterone into Δ4-abiraterone (D4A), which blocks multiple steroidogenic enzymes and antagonizes the androgen receptor.
A mutation (1245A>C) in HSD3B1 is shown to be resistant to proteasomal degradation, causing substantial accumulation of this enzyme and gain-of-function. Although the HSD3B1 (1245C) allele can be acquired by mutation, germ-line single nucleotide polymorphism (SNP; rs1047303) is also known to exist. Then, in this study, we investigated the significance of missense polymorphism in HSD3B1 gene among men treated with primary ADT or abiraterone.
The results showed men carrying variant allele showed higher risk of progression in primary androgen-deprivation therapy, but vulnerable to abiraterone treatment.
MedicalResearch.com: What should readers take away from your report?
Response: Recently, up-front abiraterone or docetaxel combined with androgen-deprivation therapy has become one of standard therapy for metastatic hormone-sensitive prostate cancer. In addition, novel antiandrogens such as enzalutamide are emerging for hormone-sensitive prostate cancer. However, the criteria choosing those agents combined with androgen-deprivation therapy has not established. From the findings in this study, HSD3B1 gene polymorphism may be a promising predictive biomarker on whether abiraterone should be utilized in combination with primary androgen-deprivation therapy.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: The finding obtained in this study should be validated in other cohorts. Especially, the significance of missense polymorphism in HSD3B1 gene should be determined in hormone-sensitive prostate cancer.
Shiota M, Narita S, Akamatsu S, et al. Association of Missense Polymorphism in HSD3B1 With Outcomes Among Men With Prostate Cancer Treated With Androgen-Deprivation Therapy or Abiraterone. JAMA Netw Open. 2019;2(2):e190115. doi:10.1001/jamanetworkopen.2019.0115
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