Nima Sharifi, MD @nimasharifimd of @CleClinicMD @ClevelandClinic discusses fundamental mechanism for other clinical outcomes and phenotypes.
In a new Cleveland Clinic-led study published in JAMA Oncology, researchers show that a testosterone-related genetic variant – HSD3B1(1245C) – is associated with more aggressive disease and shorter survival in men with metastatic prostate cancer.
This study – the first clinical trial validation of the relationship between HSD3B1 status and clinical outcomes – suggests that genetic testing for HSD3B1(1245C) may help physicians identify patients most likely to benefit from additional and more aggressive treatment.
Nima Sharifi, M.D., of Cleveland Clinic’s Lerner Research Institute, and colleagues retrospectively analyzed data from 475 participants enrolled in a large, multi-center national clinical trial testing the efficacy of androgen deprivation therapy (ADT) alone or in combination with docetaxel in prostate cancer. They compared clinical outcomes between men who carried the variant versus those who did not.
The researchers found that HSD3B1(1245C) inheritance is associated with faster progression to treatment resistance and shorter overall survival in men with low-volume metastatic prostate cancer regardless of the use of docetaxel. Interestingly, the genetic variant led to shortened survival despite the administration of any other therapies following the development of treatment resistance.
“These findings lay the groundwork for more personalized and effective treatments for prostate cancer,” said Dr. Sharifi, senior author of the study. “If men carry this specific testosterone-related genetic abnormality we may be able to individualize their therapy.”