Thursday, May 16, 2013
This week in therapeutics
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protein (Cdc42 Rac)-activated kinase 1 (PAK1)
In vitro and mouse studies suggest inhibiting PAK1 could
help treat HER2+ breast cancers. In HER2+ breast cancer cells, small hairpin RNA-mediated
knockdown of PAK1 decreased cell proliferation and CTNNB1 levels
compared with PAK2
knockdown. In mouse xenograft models for HER2+ human breast cancer, combined small molecule-mediated
inhibition of PAK1 and CTNNB1 signaling caused more potent tumor growth
prevention than inhibition of either target alone. In breast cancer cells
resistant to the HER2 inhibitor Herceptin
blockade of PAK1 and CTNNB1 restored sensitivity to the drug. Next steps
include clinical trials of PAK1 inhibitors that show favorable
Inc. unit and Chugai
Pharmaceutical Co. Ltd. market Herceptin to treat breast
and gastric cancers.
Marina Biotech Inc.'s CEQ508,
an oral RNAi targeting CTNNB1, is in Phase I/II testing to treat colorectal
Pharma Co. Ltd. and Eisai
Co. Ltd. have PRI-724,
a CTNNB1 inhibitor, in Phase I testing to treat solid tumors.
Published online May 16, 2013
Findings unpatented; mouse
models for evaluating Pak1 loss available for licensing
L.E. et al. Cancer Res.; published online April 10, 2013;
Contact: Jonathan Chernoff, Fox Chase Cancer Center, Philadelphia,
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