TopoisomeraseOvary CancerDNA Strand BreakClinical TrialRNA Polymerase IDNA damage responseIntrinsic and acquired drug resistance represent fundamental barriers to the cure of high-grade serous ovarian carcinoma (HGSC), the most common histological subtype accounting for the majority of ovarian cancer deaths....
and 2) molecular profile of tumors and predictive value of mutational signatures in predicting response or resistance to CX-5461.Clinical trial information: NCT04890613.Study cohorts and treatment arms.Main study cohortExploratory cohorthistologically-confirmed pancreatic, ovarian, prostate, or breast cance...
These results establish clinical proof-of-concept for this G-quadruplex stabilizer. Clinicaltrials.gov NCT02719977.doi:10.1038/s41467-022-31199-2Nature Publishing Group UKNature Communications
CX-5461 recently progressed through phase I clinical trial as a first-in-human inhibitor of RNA-POL I. However, we also use a comprehensive panel of in vitro and in vivo assays to demonstrate that CX-5461 has been mischaracterized and that its primary target at pharmacologically relevant ...
While their data are interesting, there are multiple lines of evidence indicating that as a therapeutic agent CX-5461 exhibits clinical properties quite different from known Top2α poisons. Both typical (e.g., Doxorubicin, Etoposide) or atypical (e.g., Vosaroxin) Top2α poisons share very ...