custirsen + mitoxantrone

Custirsen + mitoxantrone is a combination therapy investigated primarily for advanced prostate cancer. Custirsen is a second-generation antisense oligonucleotide that targets and inhibits the expression of clusterin, a cytoprotective protein upregulated in many cancers and associated with resistance to chemotherapy and poor prognosis. By binding to clusterin mRNA, custirsen reduces its translation, thereby lowering clusterin protein levels and enhancing tumor cell sensitivity to apoptosis induced by chemotherapeutic agents. Mitoxantrone is an anthracenedione antineoplastic agent that intercalates into DNA, causing crosslinks and strand breaks, inhibiting both DNA and RNA synthesis. It also acts as a type II topoisomerase inhibitor. The combination has been studied in metastatic castration-resistant prostate cancer (mCRPC), where inhibition of clusterin by custirsen was hypothesized to enhance the cytotoxic effects of mitoxantrone[2][3][4][5][6][8].