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Cardiff Oncology Announces Data Showing the Combination of PARP Inhibition with Onvansertib Overcomes PARP Inhibitor Resistance in BRCA1-mutant and Wildtype Patient-Derived Xenograft Ovarian Cancer Models
- Combining onvansertib with the PARP inhibitor (PARPi) olaparib led to statistically significant survival benefits compared to treatment with either agent
About this update from Cardiff Oncology, Inc.
[{"type":"text","content":"- Combining onvansertib with the PARP inhibitor (PARPi) olaparib led to statistically significant survival benefits compared to treatment with either agent alone in PARPi-resistant ovarian cancer models\n- Onvansertib-olaparib combination was well tolerated in vivo\nSAN DIEGO, April 8, 2022 /PRNewswire/ -- Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, today announced the results of preclinical studies evaluating the anti-cancer activity of onvansertib in combination with the PARP inhibitor (PARPi) olaparib in PARPi-resistant patient-derived xenograft (PDX) ovarian cancer models. The results are featured in a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting, which is taking place both virtually and in-person at the Ernest N. Morial Convention Center in New Orleans, Louisiana from April 8-13, 2022.\n\n \n \n \n \n \n \n\n \n\"In these studies, we sought to evaluate how combining onvansertib with PARP inhibition, an approved maintenance treatment for ovarian cancer, might mitigate the known phenomenon of acquired tumor resistance to PARP inhibitors,\" said Tod Smeal, Ph.D., chief scientific officer at Cardiff Oncology. \"We are very pleased with the results, which showed onvansertib and olaparib synergistically combining to generate strong activity against PARPi-resistant patient-derived ovarian cancer models. Given the current lack of effective treatment options for patients showing PARPi resistance, we believe these data are supportive of evaluating this combination within a PARPi-resistant clinical setting.\"\nPreclinical studies featured in the AACR poster evaluated onvansertib-olaparib combination treatment in three olaparib-resistant patient-derived xenograft (PDX) ovarian cancer models. Two of the three PDX models used (MNHOC22, MNHOC266) were cisplatin-sensitive with a mutated BRCA1 gene, while the third (MNHOC316DDP) was cisplatin-resistant with wild type BRCA1. BRCA1-mutant tumor cells are deficient for homologous recombination (HR)-mediated DNA repair and are initially sensitive to PARPi. This suggests that PARPi resistance was acquired in the MNHOC22 and MNHOC266 tumors due to the restoration of HR-mediated DNA repair, while being naturally conferred in MNHOC316DDP tum...