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Perspectives
Selective Pharmacologic Activation of the p53-Dependent Pathway as a Therapeutic Strategy for Hematologic Malignancies
Thorsten Stühmer and Ralf C. Bargou
volume 5 | issue 1
1 january 2006Pages: 39 - 42
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Most of the drugs currently used to treat hematologic cancers are genotoxic agents that exert some of their antitumor activity through p53-dependent mechanisms. However, this activity is achieved at the price of collateral genotoxic damage, which may lead to generation of more malignant tumor subclones and secondary neoplasias. Because p53 remains wild-type in the majority of hematologic malignancies nongenotoxic induction of the p53-pathway is an attractive therapeutic strategy for this group of cancers. Following the recent development of selective small-molecule MDM2-antagonists (nutlins), we have demonstrated that nutlintreatment of primary tumor cells isolated from patients with multiple myeloma induces p53 target genes and efficiently drives these cells into apoptosis. Because the apoptotic function of p53 appears to be preserved in a number of common hematologic neoplasias it should be used to investigate the utility of nongenotoxic p53-induction therapies.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.