rDNA Chromatin Activity Status as a Biomarker of Sensitivity to the RNA Polymerase I Transcription Inhibitor CX-5461
Jinbae Son, Katherine M Hannan, Gretchen Poortinga, Nadine Hein, Donald P Cameron, Austen RD Ganley, Karen E Sheppard, Richard B Pearson, Ross D Hannan, Elaine Sanij
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | FRONTIERS MEDIA SA | Published : 2020
Hyperactivation of RNA polymerase I (Pol I) transcription of ribosomal RNA (rRNA) genes (rDNA) is a key determinant of growth and proliferation and a consistent feature of cancer cells. We have demonstrated that inhibition of rDNA transcription by the Pol I transcription inhibitor CX-5461 selectively kills tumor cells in vivo. Moreover, the first-in human trial of CX-5461 has demonstrated CX-5461 is well-tolerated in patients and has single-agent anti-tumor activity in hematologic malignancies. However, the mechanisms underlying tumor cell sensitivity to CX-5461 remain unclear. Understanding these mechanisms is crucial for the development of predictive biomarkers of response that can be util..View full abstract
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Awarded by National Health and Medical Research Council (NHMRC) of Australia
Awarded by New Zealand Marsden Fund
This work was supported by the National Health and Medical Research Council (NHMRC) of Australia project grants (#1100654 and #1162052). RH and RP were supported by NHMRC fellowships. AG was supported by the New Zealand Marsden Fund (14-MAU-053).