Author Interviews, Genetic Research, JAMA, Prostate Cancer / 24.02.2019
Genetic Mutation May Predict Outcomes of Prostate Cancer Treated With Androgen-Deprivation Therapy or Abiraterone
MedicalResearch.com Interview with:
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Dr. Shiota[/caption]
Masaki Shiota MD, PhD
Department of Urology
Graduate School of Medical Sciences
Kyushu University
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.
Dr. Shiota[/caption]
Masaki Shiota MD, PhD
Department of Urology
Graduate School of Medical Sciences
Kyushu University
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.
Dr. Jagpreet Chhatwal[/caption]
Jagpreet Chhatwal PhD
Assistant Professor, Harvard Medical School
Senior Scientist, Institute for Technology Assessment
Massachusetts General Hospital
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Dr. Kitchener[/caption]
Professor Henry Kitchener, MD FRCOG FRCS
University of Manchester, Manchester, UK
MedicalResearch.com: What is the background for this study?
Response: We now have reliable and affordable technologies to detect human papillomavirus (HPV), a virus which is universally accepted as the cause of cervical cancer. Various large trials confirmed that cervical screening could be improved by replacing the smear (cytology) test that has been in use for decades, with HPV testing. Many countries are now making the switch. In England, this is planned for the end of 2019. To test how to run HPV testing within the English National Health Service, a pilot was initiated in 2013 in six screening laboratories. We also wanted to determine whether the encouraging findings from the trials could be translated to everyday practice. This is important not only because we will be using different HPV tests, but also because women undergoing screening in trials are much more selected than those who are invited to population-based screening.
Dr. Kishan[/caption]
Amar U. Kishan, MD
Assistant Professor
Department of Radiation Oncology
University of California, Los Angeles
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Typical external beam radiation courses range up to 8-9 weeks in length (39-45 treatments). There are data that shorter courses, delivering a higher dose per day, may be just as effective.
Stereotactic body radiotherapy (SBRT) really pushes this concept by condensing the treatment to just four to five treatments, with a high dose per day.
Here, we present the pooled results of the outcomes of 2142 men with low and intermediate risk prostate cancer and a median of 6.9 years of followup.
We demonstrate a very favorable efficacy and safety profile. Specifically, the rates of recurrences were 4.5% and 10.2% for low and intermediate risk disease at 7 years, and rates of late severe toxicity were 2.4% for urinary toxicity and 0.4% for gastrointestinal toxicity.
