Novel RNA Polymerase I Inhibitor CX-5461 Exhibits Antitumor Activity in Multiple Myeloma
Received Date: Apr 14, 2022 / Published Date: Jun 20, 2022
Abstract
rDNA transcription is steadily dysregulated in multiple myeloma, through oncogenes and anti-tumor routes, and particularly by c-Myc. The main downstream goals of c-Myc involve ribosomal biogenesis to enhance the protein translation capacity necessary to support the growth and self-renewal programs of malignancy cells. In the research of therapeutics to improve cancer treatment, the last 10 years have shown a renewed interest in targeting ribosome biogenesis. In the present study, we have demonstrated promise for CX-5461 as a new therapeutic target in multiple myeloma. We report that CX-5461 irreversibly inhibits ribosomal RNA (rRNA) transcription by arresting RNA polymerase I (RPI/Pol1/PolR1) in a transcription initiation complex causing down regulation of 47S and inducing the ribosomal stress. We showed that CX-5461 upregulated p53 pathway, and down regulated c-Myc causing cell cycle arrest and cell death
Keywords: CX-5461; TP53; Multiple myeloma; Cell cycle; 47S
Citation: Tagoug A, Novel RNA Polymerase I Inhibitor CX-5461 Exhibits Antitumor Activity in Multiple Myeloma. J Oncol Res Treat 7: 189.
Copyright: © 2022 Tagoug A. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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