TARGETING NUCLEOLAR DNA DAMAGE RESPONSE AS A NOVEL THERAPEUTIC STRATEGY FOR HIGH GRADE SEROUS OVARIAN CANCER

Grant number: 1162052 | Funding period: 2019 - 2022

Completed

Abstract

New therapies are required to improve outcomes for patients with ovarian cancer. In this proposal, we will optimise and validate the effectiveness of a new class of drugs we have discovered and developed to selectively damage the DNA of cancer cells, resulting in death of the cancers while sparing normal tissue.

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Ribosomal proteins and human diseases: molecular mechanisms and targeted therapy

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Harnessing the Nucleolar DNA Damage Response in Cancer Therapy

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The nucleoli are subdomains of the nucleus that form around actively transcribed ribosomal RNA (rRNA) genes. They serve as the sit..

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CX-5461 can destabilize replication forks in PARP inhibitor-resistant models of ovarian cancer

Jiachen Xuan, Richard B Pearson, Elaine Sanij

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Acquired drug resistance leads to poor clinical outcome in high grade serous ovarian cancer (HGSOC). We have demonstrated the effi..

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rDNA Chromatin Activity Status as a Biomarker of Sensitivity to the RNA Polymerase I Transcription Inhibitor CX-5461

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Hyperactivation of RNA polymerase I (Pol I) transcription of ribosomal RNA (rRNA) genes (rDNA) is a key determinant of growth and ..

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CX-5461 activates the DNA damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancer

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Acquired resistance to PARP inhibitors (PARPi) is a major challenge for the clinical management of high grade serous ovarian cance..