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The battle between tumor suppressors: is gene therapy using p16(INK4a) more efficacious than p53 for treatment of ovarian carcinoma?
Clin Cancer Res. 2001 Jun;7(6) :1487-9
PMID: 11410480 URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11410480
AbstractThe present study offers a well-controlled and compelling comparison of the ability of different tumor suppressor proteins to work in gene therapeutic approaches. Future questions seem clear. Specifically, what is the requirement for pRB for tumor suppression by p16INK4a in vivo? Additionally, what is the contribution, if any, of the pRB family members p107 and p130 to growth suppression by this protein? Finally, the ability of the p16INK4a adenovirus to synergize with chemotherapeutic drugs needs to be determined. It seems unlikely that gene therapy alone will be efficacious, so it becomes important to define drugs that will enhance the efficacy of this avenue. Finding such a drug may be more difficult than imagined; adenoviral-mediated delivery of p16INK4a has already been demonstrated to render tumor cells chemoresistant to agents commonly used in ovarian cancer, such as cisplatin and paclitaxel (21) . Therefore, it will be important to identify drugs or therapies whose mechanism of action is not inhibited by p16INK4a (one possibility is radiotherapy; Ref. 22 ) and to compare these drugs in combination with gene therapy with the standard treatments for this tumor type. Additionally, the standard hurdles for gene therapy modalities, such as antiviral immune response and improved target cell specificity, need to be overcome. Finally, there is compelling need for a mouse model of spontaneous ovarian carcinoma. Such a model, in which oncogenic transgenes are driven by promoters that are largely restricted to the ovarian surface epithelium, such as the ovarian specific 1 promoter (23) , will greatly facilitate the discovery of novel mechanisms of detection and treatment for ovarian cancer.
Notes1078-0432 Comment Journal Article