CX-5461 Sensitizes DNA Damage Repair-proficient Castrate-resistant Prostate Cancer to PARP Inhibition.
Mitchell G Lawrence, Laura H Porter, Nicholas Choo, David Pook, Jeremy P Grummet, Carmel J Pezaro, Shahneen Sandhu, Susanne Ramm, Jennii Luu, Andrew Bakshi, David L Goode, Elaine Sanij, Richard B Pearson, Ross D Hannan, Kaylene J Simpson, Renea A Taylor, Gail P Risbridger, Luc Furic
Mol Cancer Ther | Published : 2021
Monotherapy with PARP inhibitors is effective for the subset of castrate-resistant prostate cancer (CRPC) with defects in homologous recombination (HR) DNA repair. New treatments are required for the remaining tumors, and an emerging strategy is to combine PARP inhibitors with other therapies that induce DNA damage. Here we tested whether PARP inhibitors are effective for HR-proficient CRPC, including androgen receptor (AR)-null tumors, when used in combination with CX-5461, a small molecule that inhibits RNA polymerase I transcription and activates the DNA damage response, and has antitumor activity in early phase I trials. The combination of CX-5461 and talazoparib significantly decreased ..View full abstract
Awarded by Cass Foundation
Awarded by Victorian Cancer Agency
Awarded by DOD | United States Army | MEDCOM | CDMRP | DOD Prostate Cancer Research Program
Awarded by Department of Health, Australian Government | National Health and Medical Research Council