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Signal therapy of NF1-deficient tumor xenograft in mice by the anti-PAK1 drug FK228

Item Type:Article
Title:Signal therapy of NF1-deficient tumor xenograft in mice by the anti-PAK1 drug FK228
Creators Name:Hirokawa, Y. and Nakajima, H. and Hanemann, C.O. and Kurtz, A. and Frahm, S. and Mautner, V. and Maruta, H.
Abstract: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 p21WAF1, that block upstream and downstream of PAK1, respectively. Here we demonstrate that (1) 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 (2) 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.
Keywords:FK228, Neurofibromatosis, NF1, PAK1, Animals, Mice
Source:Cancer Biology & Therapy
Publisher:Landes Bioscience
Page Range:379-381
Date:1 April 2005
Official Publication:https://doi.org/10.4161/cbt.4.4.1649
PubMed:View item in PubMed

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