Zytiga (abiraterone acetate) and Ketoconazole (keto) are both widely used in prostate cancer therapy to treat men with advanced prostate cancer. They both have a common mechanism of action, they both work by inhibiting the enzyme CYP17 that is responsible for androgen biosynthesis (creation). Inhibiting CYP17 lowers testosterone levels, which results in prostate cancer tumor regression.
Because of these drugs similar mechanism of action Zytiga is often compared to keto (FDA approved as an antifungal and not for prostate cancer). Both, when used to treat advanced prostate cancer that is hormone refractory (no longer responding to first line hormone therapy or castrate resistant prostate cancer) operate on the same molecular target enzyme, CYP17.
However, there are some very significant differences between these two drugs. Keto binds to the CYP17 molecule, however it often becomes unbound and then ineffective as a treatment option. The amount of ketoconazole bound to CYP17 molecules depends on the concentration of ketoconazole in the cell at any point in time, so shifts in drug levels effects keto’s binding ability. On the other hand, Zytiga is a specific (“selective”), potent, and irreversible inhibitor of CYP17. By contrast, once abiraterone acetate binds to a molecule of CYP17, that particular molecule of CYP17 is permanently disabled.
Zytiga is considered superior to keto as it is significantly more powerful. Keto, being non-