The role of antisense oligonucleotides in the treatment of bladder cancer.
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.
Duggan
Brian J
BJ
Department of Urology and Quantitative Pathology, Belfast City Hospital, Belfast, BT12 6BL, Northern Ireland. bjduggan71@hotmail.com
Gray
Sam
S
Johnston
Samuel R
SR
Williamson
Kate
K
Miyaki
Hideaki
H
Gleave
Martin
M
D017209:Apoptosis; D015198:Designer Drugs; D019254:Genes, bcl-2 / Q000235:genetics; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000009:adverse effects / Q000235:genetics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D017211:Treatment Failure; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy
D015198:Designer Drugs; D016376:Oligonucleotides, Antisense