title: Targeting RNA polymerase I to treat MYC-driven cancer.
abstract: The MYC oncoprotein and transcription factor is dysregulated in a majority of human cancers and is considered a major driver of the malignant phenotype. As such, developing drugs for effective inhibition of MYC in a manner selective to malignancies is a 'holy grail' of transcription factor-based cancer therapy. Recent advances in elucidating MYC biology in both normal cells and pathological settings were anticipated to bring inhibition of tumorigenic MYC function closer to the clinic. However, while the extensive array of cellular pathways that MYC impacts present numerous fulcrum points on which to leverage MYC's therapeutic potential, identifying the critical target(s) for MYC-specific cancer therapy has been difficult to achieve. Somewhat unexpectedly, MYC's fundamental role in regulating the 'housekeeping' process of ribosome biogenesis, one of the most ubiquitously required and conserved cell functions, may provide the Achilles' heel for therapeutically targeting MYC-driven tumors.
authors.affiliation: 1] Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia [2] Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia [3] Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, Victoria, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Poortinga
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: L M
authors.initials: LM
authors.lastname: Quinn
authors.affiliation: 1] Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia [2] Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia [3] Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Victoria, Australia [4] Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia [5] School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: R D
authors.initials: RD
authors.lastname: Hannan
mesh_terms: D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D051736:Proto-Oncogene Proteins c-mdm2 / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors / Q000502:physiology*; D012318:RNA Polymerase I / Q000037:antagonists & inhibitors* / Q000502:physiology; D012270:Ribosomes / Q000187:drug effects / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2; D012318:RNA Polymerase I