Journal article

Targeting RNA Polymerase I transcription synergises with TOP1 inhibition in potentiating the DNA damage response in high-grade serous ovarian cancer

Shunfei Yan, Piyush Madhamshettiwar, Kaylene Simpson, Sarah Ellis, Jian Kang, Carleen Cullinane, Karen Sheppard, Katherine Hannan, Ross Hannan, Elaine Sanij, Richard Pearson, Keefe Chan

Published : 2019

Abstract

Abstract Limited effective therapeutic options are available for patients with recurrent high-grade serous carcinoma (HGSC), the most common histological subtype accounting for the majority of ovarian cancer deaths. We have shown efficacy in poly-ADP ribose polymerase (PARP) inhibitor-resistant HGSC for the RNA Polymerase I (Pol I) transcription inhibitor CX-5461 through its ability to activate a nucleolar-associated DNA damage response (DDR). Here, we screen the protein-coding genome to identify potential targets whose inhibition enhances the efficacy of CX-5461. We identify a network of cooperating inhibitory interactions, including components of homologous recombination (HR) DNA repair an..

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