Small Inhibitor May Boost Effectiveness of PARP Inhibitors in Some Ovarian Cancers, Mouse Study Finds

Small Inhibitor May Boost Effectiveness of PARP Inhibitors in Some Ovarian Cancers, Mouse Study Finds
A small inhibitor that prevents cells from making ribosomes — the machinery used to produce proteins — may improve the effectiveness of PARP inhibitors in ovarian cancers with mutations in DNA repair genes, a study in mice found. This inhibitor is a promising approach for ovarian cancers that are no longer susceptible to platinum-based chemotherapy or PARP inhibitors. The study with this finding, "CX-5461 activates the DNA damage response anddemonstrates therapeutic efficacy in high-gradeserous ovarian cancer," was published in Nature Communications. PARP inhibitors such as Lynparza (olaparib) or Zejula (niraparib), are ovarian cancer treatments that block enzymes needed for adequately correcting DNA errors in cells, preventing cancer cells from repairing their DNA, and ultimately causing their death. Despite their increasing use in ovarian cancer patients, there are cases of resistance to these treatments, and researchers have been working to find strategies to overcome such resistance. CX-546 is a small molecule inhibitor that targets the polimerase I enzyme, which is needed to produce ribosomal RNA molecules. This inhibitor has shown promise in some blood cancers and also is in a Phase 1 clinical trial (NCT02719977) of solid tumors. CX-546 also induces DNA damage and, much like PARP inhibitors, it works particularly well in cancers carrying mutations in DNA repair genes, but the two approaches appear to work via distinct biological mechanisms. Researchers at Peter MacCallum Cancer Center, John Curtin School of Medical Research, and Walter and Eliza Hall Institute of Medical Research, all in Australia, now examined the exact mechanisms used by this novel small molecule inhibitor, and whether it could be used in combination with approved ther
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