Custirsen (OGX-011): clusterin inhibitor in metastatic prostate cancer

Adenocarcinoma of the prostate is the most common cancer in men in the Western Hemisphere. This diagnosis includes a clinicopathologically diverse collection of disease entities, encompassing a spectrum from early localized disease to advanced-stage castration-sensitive and ultimately metastatic, castration-resistant states. Although early-stage disease is treatable and potentially curable, treatment options for castration-resistant prostate cancer, the common pathway to prostate cancer death, remain limited and palliative in nature. Therapeutic resistance to androgen blockade, cytotoxic chemotherapy, and radiotherapy is underpinned by a number of cellular mechanisms. The upregulation of protective, antiapoptotic chaperone proteins is one of these mechanisms, and is exemplified by the protein clusterin in castration-resistant prostate cancer. Antisense oligonucleotide technology provides the potential to inhibit specific genes in cancer cells and with this the possibility of a vast impact in oncology, but no antisense drugs have been approved for use in cancer patients to date. Custirsen (OGX-011) is a novel antisense oligonucleotide drug which targets clusterin expression, and its application in prostate cancer is reviewed in this article.