Intratumoral De Novo Steroid Synthesis Activates Androgen Receptor in Castration-Resistant Prostate Cancer and Is Upregulated by Treatment with CYP17A1 Inhibitors

The study from 2011 explored how castration-resistant prostate cancer (CRPC) cells can activate the androgen receptor (AR) through intratumoral de novo steroid synthesis, and how this process is affected by CYP17A1 inhibitors like abiraterone. The researchers discovered that CRPC cells can produce androgens internally, which allows them to continue stimulating the AR even after treatments aimed at reducing androgen levels. They also found that treatment with abiraterone could lead to an increase in CYP17A1 expression, suggesting a mechanism for the development of resistance to this therapy. Additionally, the study indicated that CRPC cells with a specific AR mutation (T877A) were not dependent on CYP17A1 but still relied on steroid synthesis via CYP11A1. The findings imply that therapies targeting the broader steroid synthesis pathway could be effective against CRPC, including cases resistant to CYP17A1 inhibitors. However, the document did not provide the total number of mice or cells used in the study, which is important for assessing the strength of the findings.