Small Molecule Inhibition of Group I p21-Activated Kinases in Breast Cancer Induces Apoptosis and Potentiates the Activity of Microtubule Stabilizing Agents

Christy C Ong; Sarah Gierke; Cameron Pitt; Meredith Sagolla; Christine K Cheng; Wei Zhou; Adrian M Jubb; Laura Strickland; Maike Schmidt; Sergio G Duron; David A Campbell; Wei Zheng; Seameen Dehdashti; Min Shen; Nora Yang; Mark L Behnke; Wenwei Huang; John C McKew; Jonathan Chernoff; William F Forrest; Peter M Haverty; Suet-Feung Chin; Emad A Rakha; Andrew R Green; Ian O Ellis; Carlos Caldas; Thomas O'Brien; Lori S Friedman; Hartmut Koeppen; Joachim Rudolph; Klaus P Hoeflich


Breast Cancer Res. 2015;17(59) 

In This Article


PAKs have been implicated in various aspects of tumorigenesis. In this study, we demonstrate that PAK1 amplification and overexpression are associated with poor clinical outcome in a large collection of luminal breast cancers. Treatment of PAK1-amplified breast cancer cells with a novel small molecule inhibitor of group I PAKs, FRAX1036, resulted in apoptosis. Efficacy was also potentiated in combination with microtubule inhibitors that are used as standard-of-care chemotherapy in advanced breast cancer. Taken together, our findings support the further therapeutic evaluation of PAK inhibitors in breast cancer.