Journal article

The Dual Inhibition of RNA Pol I Transcription and PIM Kinase as a New Therapeutic Approach to Treat Advanced Prostate Cancer

Richard J Rebello, Eric Kusnadi, Donald P Cameron, Helen B Pearson, Analia Lesmana, Jennifer R Devlin, Denis Drygin, Ashlee K Clark, Laura Porter, John Pedersen, Shahneen Sandhu, Gail P Risbridger, Richard B Pearson, Ross D Hannan, Luc Furic



PURPOSE: The MYC oncogene is frequently overexpressed in prostate cancer. Upregulation of ribosome biogenesis and function is characteristic of MYC-driven tumors. In addition, PIM kinases activate MYC signaling and mRNA translation in prostate cancer and cooperate with MYC to accelerate tumorigenesis. Here, we investigate the efficacy of a single and dual approach targeting ribosome biogenesis and function to treat prostate cancer. EXPERIMENTAL DESIGN: The inhibition of ribosomal RNA (rRNA) synthesis with CX-5461, a potent, selective, and orally bioavailable inhibitor of RNA polymerase I (Pol I) transcription, has been successfully exploited therapeutically but only in models of hematologic ..

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Awarded by Cancer Australia

Awarded by Prostate Cancer Foundation of Australia

Awarded by National Health and Medical Research Council

Funding Acknowledgements

This work was supported by Cancer Australia (CA 1084546 to R.D. Hannan, R.B. Pearson, G.P. Risbridger, and L. Furic); Prostate Cancer Foundation of Australia (YI 0310 to L. Furic and CG 1511 to R.B. Pearson, R.D. Hannan, and L. Furic and YIA to S. Sandhu); National Health and Medical Research Council (Program Grant 1053792 and Project Grant 1004881 to R.B. Pearson and R.D. Hannan; Senior Research Fellowships to R.B. Pearson and R.D. Hannan and Senior Principal Research Fellowship APP1102752 to G.P. Risbridger).