ABSTRACT
A prodrug is an inactive and less toxic agent than the bioactivated agent derived from the prodrug. Typically, the prodrug is bioactivated by an enzyme such as an esterase. The use of prodrugs to treat cancer is a widely accepted pharmacologic strategy but has yet to achieve widespread clinical utilization. Rapid advances in bioinformatics provide the opportunity to accelerate treatment options for cancer by focusing on the rational design, and subsequent organic synthesis, of prodrugs likely to be good substrates for a bioactivating target enzyme. Quite remarkably, many cancer cells, including tumorigenic prostate cancer cells, exhibit a high level of intrinsic oxidative stress. Akt activation is commonly caused by mutations in components of its signaling cascade and results in cancer cell lines with an increased ability to escape normal apoptosis and proliferate. Drugs that inhibit the proteasome are thought to have anticancer effects by permitting the accumulation of toxic misfolded/oxidized proteins which induce apoptosis.
