The dual inhibition of RNA Pol I transcription and PIM kinase as a new therapeutic approach to treat advanced prostate cancer

RJ Rebello; E Kusnadi; DP Cameron; HB Pearson; A Lesmana; JR Devlin; D Drygin; AK Clark; L Porter; J Pedersen; S Sandhu; GP Risbridger; RB Pearson; RD Hannan; L Furic

Journal article

The dual inhibition of RNA Pol I transcription and PIM kinase as a new therapeutic approach to treat advanced prostate cancer

RJ Rebello, E Kusnadi, DP Cameron, HB Pearson, A Lesmana, JR Devlin, D Drygin, AK Clark, L Porter, J Pedersen, S Sandhu, GP Risbridger, RB Pearson, RD Hannan, L Furic

Clinical Cancer Research | AMER ASSOC CANCER RESEARCH | Published : 2016

DOI: 10.1158/1078-0432.CCR-16-0124

Abstract

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 ribosomalRNA (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 m..

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Richard Rebello Author

Richard Pearson Author

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Grants

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).