The presence of oligoclonality has implications for the potential efficacy of novel molecular therapeutic agents for bladder cancer. The molecular targets for such therapies must be widely sampled in a tumor population to assess expression in separate clones.

Both intravesical and systemic chemotherapy are limited in their efficacy in the treatment of bladder cancer patients. These limitations are centred around an inability to induce apoptosis in bladder tumour cells. This resistance to apoptosis induction is commonly associated with the overexpression of antiapoptotic proteins such as Bcl-2. Strategies to decrease the cellular expression of such proteins would enhance chemotherapy effectiveness. One such strategy is to use antisense oligonucleotides which are short sequence specific single stranded DNA or RNA molecules designed to bind to the RNA of the target protein. By binding to the target RNA, protein production is interrupted and target protein levels decease. When used to target antiapoptotic proteins, antisense oligonucleotides can therefore be used as a pre-treatment before chemotherapy to help chemosensitise the tumour cell. This review outlines the rationale for this strategy and the work done to date with antisense oligonucleotides in bladder cancer.

This review examines the role that antisense oligonucleotides play in the treatment of superficial and muscle-invasive bladder cancer. The unique environment of the urinary bladder allows intravesical instillation of antisense oligonucleotides, and researchers have already demonstrated uptake of antisense oligonucleotides in models of bladder cancer. Second, proof of principle has been established by demonstrating downregulation of the antisense target mRNA and protein. Third, and most importantly from a therapeutic perspective, synergy between chemotherapy and antisense oligonucleotides has been shown in bladder cancer models in vitro and in vivo. The collective evidence points to a role for antisense oligonucleotides in the treatment of superficial and muscle-invasive bladder cancer in combination with existing treatment modalities.

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