A NEW APPROACH TO TARGETING CELL GROWTH FOR THE TREATMENT OF CANCER
Grant number: 1038852 | Funding period: 2012 - 2014
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)
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
RNA polymerase I (Pol I) transcription of ribosomal RNA genes (rDNA) is tightly regulated downstream of oncogenic pathways, and it..
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
Dysregulation of RNA polymerase I (Pol I)-dependent ribosomal DNA (rDNA) transcription is a consistent feature of malignant transf..
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
BACKGROUND: Recent studies have highlighted the fundamental role that key oncogenes such as MYC, RAS and PI3K occupy in driving RN..
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
Exquisite control of ribosome biogenesis is fundamental for the maintenance of cellular growth and proliferation. Importantly, syn..
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
Upstream Binding Factor (UBF) is a unique multi-HMGB-box protein first identified as a co-factor in RNA polymerase I (RPI/PolI) tr..