custirsenOGX011

Custirsen, also known as OGX-011, is an antisense oligonucleotide developed by OncoGenex Pharmaceuticals. It is designed to target clusterin, a stress-induced protein implicated in cancer cell survival and resistance to chemotherapy and radiotherapy. By reducing the production of clusterin, custirsen aimed to sensitize tumor cells to standard cancer treatments.

Mechanism and design: Custirsen is a chemically modified antisense oligonucleotide intended to bind to the mRNA transcript of clusterin and promote its degradation, thereby lowering clusterin protein levels. In clinical settings, it was delivered systemically by intravenous infusion and used in combination with conventional anticancer therapies on schedules compatible with those regimens.

Clinical development: OGX-011 was evaluated in phase II and phase III trials across several solid tumors, with its most advanced development in metastatic castration-resistant prostate cancer (mCRPC) in combination with docetaxel and other agents. Trials sought to determine whether suppressing clusterin could improve response rates, progression-free survival, or overall survival. Across studies, results were mixed, and the program did not achieve the regulatory endpoints needed for approval.

Status: By the mid-2010s, the custirsen program did not reach regulatory approval, and development from the sponsor was largely discontinued. While custirsen itself did not become an approved therapy, clusterin continues to be recognized in cancer biology as a potential co-target to enhance the effectiveness of existing treatments.