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The Phosphoinositide 3-Kinase/Akt1/Par-4 Axis: A Cancer-Selective Therapeutic Target

Departments of ¹ Radiation Medicine and ² Microbiology, Immunology and Molecular Genetics; ³ Graduate Center for Toxicology; and ⁴ Markey Cancer Center, University of Kentucky, Lexington, Kentucky

Requests for reprints: Vivek M. Rangnekar, Department of Radiation Medicine, University of Kentucky, Combs Research Building, Room 303, 800 Rose Street, Lexington, KY 40536. Phone: 859-257-2677; Fax: 859-257-9608; E-mail: vmrang01{at}pop.uky.edu.

Activation of the phosphoinositide 3-kinase (PI3K)/Akt cell survival pathway in many cancers makes it an appealing target for therapeutic development. However, because this pathway also has an important role in the survival of normal cells, tactics to achieve cancer selectivity may prove important. We recently showed that the cancer-selective proapoptotic protein Par-4 is a key target for inactivation by PI3K/Akt signaling. Additionally, we found that Par-4 participates in mediating apoptosis by PTEN, the tumor suppressor responsible for blocking PI3K/Akt signaling. As a central player in cancer cell survival, Par-4 may provide a useful focus for the development of cancer-selective therapeutics. (Cancer Res 2006; 66(6): 2889-92)

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