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Brief Communication
Signal Therapy of NF1-deficient Tumor Xenograft in Mice by the Anti-PAK1 Drug FK228
Yumiko Hirokawa, Hidenori Nakajima, C. Oliver Hanemann, Andreas Kurtz, Silke Frahm, Victor Mautner and Hiroshi Maruta
volume 4 | issue 4
April 2005Pages: 379-381
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PAK1, a Rac/CDC42-dependent Ser/Thr kinase, is required for the malignant growth of RAS transformants as well as both NF1-deficient and NF2-deficient cancer cells. FK228, a histone deacetylase (HDAC) inhibitor, suppresses the growth of more than 70% of human cancers in vivo including RAS transformants, breast cancers and prostate cancers by activating a set of genes including the tumor suppressors gelsolin and p21/WAF1, that block up-stream and down-stream of PAK1, respectively. Here we demonstrate that (i) the anti-PAK1 drug FK228 (0.1 nM) completely blocks the growth of both NF1-deficient and NF2-deficent cancer cells in vitro, and that (ii) FK228 (2.5 mg/kg, i.p., twice a week) causes the complete regression of an NF1-deficient human malignant peripheral nerve sheath tumor (MPNST) xenograft in nude mice. This is the very first case where a chemical drug in clinical trials for cancers has ever worked so effectively on neurofibromatosis (experimental neurofibromas) in vivo.
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 PDFIf 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.