The role of clusterin in prostate cancer: treatment resistance and potential as a therapeutic target.

Resistance to cancer treatment can arise through multiple mechanisms and negatively impacts on progression rates and survival times. New therapies targeting pathways underlying resistance would improve treatment outcomes and be of particular value in the treatment of prostate cancer, many of whom develop tumors refractory to radiation, hormonal therapy and chemotherapy regimens. The improved understanding of metastatic castration resistant prostate cancer progression mechanisms has broadened the therapeutic window by unveiling multiple molecular targets. Several approaches are being investigated to overcome resistance in prostate cancer, including the use of novel taxanes and tubulin inhibitors, and the inhibition of cell survival pathways. This review focuses on clusterin, a small heat-shock-like protein that is overexpressed in many types of solid tumors; we summarize the preclinical and clinical evidence supporting the rationale for targeting clusterin as a means to resensitize prostate tumors to radiation and chemotherapy agents.