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Targeting the RNA Polymerase I Transcription for Cancer Therapy Comes of Age

  1. Author:
    Ferreira, Rita
    Schneekloth,Jay
    Panov, Konstantin I.
    Hannan, Katherine M.
    Hannan, Ross D.

  2. Author Address

    Australian Natl Univ, John Curtin Sch Med Res, ACRF Dept Canc Biol & Therapeut, Acton, NSW 2601, Australia.NCI, Chem Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA.Queens Univ Belfast, Med Biol Ctr, Sch Biol Sci, CCRCB, Belfast BT9 7BL, Antrim, North Ireland.Queens Univ Belfast, Sch Biol Sci, Belfast BT9 7BL, Antrim, North Ireland.Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic 3010, Australia.Peter MacCallum Canc Ctr, 305 Grattan St, Melbourne, Vic 3000, Australia.Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia.
    1. Year: 2020
    2. Date: FEB
    3. Epub Date: 2020 01 21
  2. Journal: Cells
  3. MDPI,
    1. 9
    2. 2
  5. Type of Article: Review
  6. Article Number: 266
  7. ISSN: 2073-4409
  1. Abstract:

    Transcription of the ribosomal RNA genes (rDNA) that encode the three largest ribosomal RNAs (rRNA), is mediated by RNA Polymerase I (Pol I) and is a key regulatory step for ribosomal biogenesis. Although it has been reported over a century ago that the number and size of nucleoli, the site of ribosome biogenesis, are increased in cancer cells, the significance of this observation for cancer etiology was not understood. The realization that the increase in rRNA expression has an active role in cancer progression, not only through increased protein synthesis and thus proliferative capacity but also through control of cellular check points and chromatin structure, has opened up new therapeutic avenues for the treatment of cancer through direct targeting of Pol I transcription. In this review, we discuss the rational of targeting Pol I transcription for the treatment of cancer; review the current cancer therapeutics that target Pol I transcription and discuss the development of novel Pol I-specific inhibitors, their therapeutic potential, challenges and future prospects.

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External Sources

  1. View Full Text
  2. DOI: 10.3390/cells9020266
  3. PMID: 31973211
  4. View record in Web of Science®
  5. WOS: 000521944900007

Library Notes

  1. Fiscal Year: FY2019-2020
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