A NEW APPROACH TO TARGETING CELL GROWTH FOR THE TREATMENT OF CANCER

Grant number: 1038852 | Funding period: 2012 - 2014

Completed

Abstract

We have made the fundamental discovery that ribosomal gene transcription is not simply a 'house keeping' process in cancer cells but is required to maintain malignant cell viability. Strikingly inhibition of ribosomal gene transcription using a novel small molecule inhibitor, CX-5461, shows profound selectivity for malignant cells over normal cells. This proposal will translate these observations into 'first in man' phase 1 clinical trials of CX-5461 for the treatment of blood cancers.

Related publications (5)

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First-in-Human RNA Polymerase I Transcription Inhibitor CX-5461 in Patients with Advanced Hematologic Cancers: Results of a Phase I Dose-Escalation Study

Amit Khot, Natalie Brajanovski, Donald P Cameron, Nadine Hein, Kylee H Maclachlan, Elaine Sanij, John Lim, John Soong, Emma Link, Piers Blombery, Ella R Thompson, Andrew Fellowes, Karen E Sheppard, Grant A McArthur, Richard B Pearson, Ross D Hannan, Gretchen Poortinga, Simon J Harrison

2019-08-01

RNA polymerase I (Pol I) transcription of ribosomal RNA genes (rDNA) is tightly regulated downstream of oncogenic pathways, and it..

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Amino acid-dependent signaling via S6K1 and MYC is essential for regulation of rDNA transcription

Jian Kang, Eric P Kusnadi, Allison J Ogden, Rodney J Hicks, Lukas Bammert, Ulrike Kutay, Sandy Hung, Elaine Sanij, Ross D Hannan, Katherine M Hannan, Richard B Pearson

2016-08-02

Dysregulation of RNA polymerase I (Pol I)-dependent ribosomal DNA (rDNA) transcription is a consistent feature of malignant transf..

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The nucleolus as a fundamental regulator of the p53 response and a new target for cancer therapy

Simone J Woods, Katherine M Hannan, Richard B Pearson, Ross D Hannan

2015-07-01

BACKGROUND: Recent studies have highlighted the fundamental role that key oncogenes such as MYC, RAS and PI3K occupy in driving RN..

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Regulation of rDNA transcription in response to growth factors, nutrients and energy

Eric P Kusnadi, Katherine M Hannan, Rodney J Hicks, Ross D Hannan, Richard B Pearson, Jian Kang

2015-02-01

Exquisite control of ribosome biogenesis is fundamental for the maintenance of cellular growth and proliferation. Importantly, syn..

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Conditional Inactivation of Upstream Binding Factor Reveals Its Epigenetic Functions and the Existence of a Somatic Nucleolar Precursor Body

Nourdine Hamdane, Victor Y Stefanovsky, Michel G Tremblay, Attila Nemeth, Eric Paquet, Frederic Lessard, Elaine Sanij, Ross Hannan, Tom Moss

2014-08-01

Upstream Binding Factor (UBF) is a unique multi-HMGB-box protein first identified as a co-factor in RNA polymerase I (RPI/PolI) tr..

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