Abstract P21-activated kinase (PAK) 2, a member of PAK family of serine/threonine kinases, plays an important role in physiological processes such as motility, survival, mitosis, and apoptosis. However, the role of PAK2 in chemotherapy resistance, as well as cell proliferation, is not clear. In this report, we showed that the protein expression level of PAK2 is higher in human breast cancer cell lines and human breast invasive carcinoma tissues compared with adjacent normal breast tissues. Importantly, we found that PAK2 can bind with caspase-7 and phosphorylate caspase-7 at Ser30, Thr173 and Ser239. Phosphorylation of caspase-7 decreases its activity, thereby inhibiting cellular apoptosis. Knocking down PAK2 expression can restore caspase-7 activity and promote apoptosis of MCF-7 breast cancer cells. Our data suggests that the highly expressed PAK2 mediates chemotherapy resistance in human breast invasive ductal carcinoma and that PAK2 is a novel target of chemotherapy for breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1960. doi:10.1158/1538-7445.AM2011-1960