Prostate cancer is an adenocarcinoma that initially starts as a prostatic intraepithelial neoplasia. Glutathione S-transferases (GSTP1) are detoxifying enzymes that catalyze conjunction of glutathione with harmful, electrophilic molecules, thereby protecting cells from carcinogenic factors. Cells of prostatic intraepithelial neoplasia, devoid of GSTP1, undergo DNA damage mediated by such carcinogens.
Prostate cancer is also caused by genetic alterations to tumor suppressors like PTEN, NKX3-1 and p21Kip1. These are molecules are involved in signaling pathways that regulate proliferation, survival, cell cycle progression and apoptosis in the normal prostate. Mutations in these genes leads to uncontrolled cell proliferation and inhibition of apoptosis.
The androgen receptor (AR) also plays a crucial role in both early development as well as late progression of the disease. Primary prostatic cancers are largely dependent on androgens for growth and survival. Hence most patients initially respond favorably to androgen ablation and antiandrogen therapy. However, this is often followed by the emergence of androgen-independent prostate cancer. This is associated with mutations in the AR gene that permit receptor activation by other ligands, increased expression of AR accompanying AR amplification, and ligand-independent AR activation.