Antigenic variation
Antigenic variation refers to the mechanism by which an infectious agent such as a protozoan, bacterium or virus alters its surface proteins in order to avoid a host immune response. It is related to phase variation. Immune evasion is particularly important for organisms that target long-lived hosts, repeatedly infect a single host and are easily transmittable. Antigenic variation not only enables immune evasion by the pathogen, but also allows the microbes to cause re-infection, as their antigens are no longer recognized by the host's immune system. When an organism is exposed to a particular antigen (i.e. a protein on the surface of a bacterium) an immune response is stimulated and antibodies are generated to target that specific antigen. The immune system will then "remember" that particular antigen, and defenses aimed at that antigen become part of the immune system’s acquired immune response. If the same pathogen tries to re-infect the same host the antibodies will act rapidly to target the pathogen for destruction. However, if the pathogen can alter its surface antigens, it can evade the host's acquired immune system. This will allow the pathogen to re-infect the host while the immune system generates new antibodies to target the newly identified antigen. Antigenic variation can occur by altering a variety of surface molecules including proteins and carbohydrates. There are many molecular mechanisms behind antigenic variation, including gene conversion, site-specific DNA inversions, hypermutation, as well as recombination of sequence cassettes. In all cases, antigenic variation and phase variation result in a heterogenic phenotype of a clonal population. Individual cells either express the phase-variable protein(s) or express one of multiple antigenic forms of the protein. This form of regulation has been identified mainly, but not exclusively, for a wide variety of surface structures in pathogens and is implicated as a virulence strategy.
Antiandrogen
Androgen synthesis inhibitors are enzyme inhibitors that prevent the biosynthesis of androgens. This process occurs mainly in the gonads and adrenal glands, but also occurs in other tissues like the prostate gland, skin, and hair follicles. These drugs include aminoglutethimide, ketoconazole, and abiraterone acetate. Aminoglutethimide inhibits cholesterol side-chain cleavage enzyme, also known as P450scc or CYP11A1, which is responsible for the conversion of cholesterol into pregnenolone and by extension the production of all steroid hormones, including the androgens. Ketoconazole and abiraterone acetate are inhibitors of the enzyme CYP17A1, also known as 17α-hydroxylase/17,20-lyase, which is responsible for the conversion of pregnane steroids into androgens, as well as the conversion of mineralocorticoids into glucocorticoids. Because these drugs all prevent the formation of glucocorticoids in addition to androgens, they must be combined with a glucocorticoid like prednisone to avoid adrenal insufficiency. A newer drug currently under development for treatment of prostate cancer, seviteronel, is selective for inhibition of the 17,20-lyase functionality of CYP17A1, and for this reason, unlike earlier drugs, does not require concomitant treatment with a glucocorticoid.