Researchers at the University of Colorado (UC) Denver, Anschutz Medical Campus, have discovered a novel combination treatment strategy that could offer new hope to ovarian cancer patients who stop responding to existing PARP inhibitor (PARPi) therapies. The strategy combines a PARP inhibitor, a targeted drug used to treat certain types of ovarian cancer, with a novel indirect WNT inhibitor, SM08502 (cirtuvivint), to attack cancer from two directions. SM08502 is a dual CDC-like kinase and dual-specificity tyrosine phosphorylation–regulated kinase inhibitor. In a newly reported study, the researchers report on tests evaluating therapy combining SM08502 with PARPi in multiple resistant models of homologous recombination–deficient high-grade serous carcinoma (HGSC). The team has also advanced from the laboratory to a Phase I clinical trial on the campus. “I began my career focused on understanding why ovarian cancer becomes resistant to therapy. PARP inhibitors have been a cornerstone of my research, but resistance remains a major challenge,” said Benjamin Bitler, PhD, associate professor and the D. Thomas and Kay L. Dunton Endowed Chair in Ovarian Cancer Research at CU Anschutz. “Early on, we characterized therapy-resistant cell lines, and this research represents the next step—developing strategies to help patients who may have no other options.” Bitler is senior author of the team’s published paper in Cancer Research Communications, outlining preclinical studies. In the paper, titled “SM08502-Mediated β-Catenin Repression Synergizes with Olaparib to Inhibit Tumor Progression,” the researchers concluded that their study “… provides strong preclinical evidence that SM08502, in combination with PARPi, may be an effective…
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