IN THE SPOTLIGHT New Connections between Old Pathways: PDK1 Signaling Promotes Cellular Transformation through PLK1-Dependent MYC Stabilization

Authors’ Affi liation: Department of Urology, School of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California Corresponding Author: Davide Ruggero, University of California, San Francisco, 1450 3rd Street, Helen Diller Room 386 MC 3110, San Francisco, CA 94158. Phone: 415-514-9755; Fax: 415-514-4826; E-mail: davide [email protected] doi: 10.1158/2159-8290.CD-13-0581 ©2013 American Association for Cancer Research. Summary: Limited understanding of the functional link between multiple oncogenic pathways is a major barrier in the ongoing effort of cancer biologists to design an effective therapeutic approach to treat malignancies characterized by driver oncogenic network signals. In this issue of Cancer Discovery , Tan and colleagues elucidate a novel PDK1–PLK1–MYC signaling pathway connecting two fundamental oncogenic programs, phosphoinositide 3-kinase and MYC. They defi ne the functional role for PDK1–PLK1–MYC signaling in cancer cell survival and tumor formation and show the therapeutic benefi t of inhibiting PDK1 and PLK1 pharmacologically in cancer, tackling the most undruggable tumors defi ned by elevated levels of the MYC oncoprotein. Cancer Discov; 3(10); 1099–1102. ©2013 AACR.