Screening a living biobank identifies cabazitaxel as a strategy to combat acquired taxol resistance in high-grade serous ovarian cancer.

ABSTRACT: The anti-mitotic agent taxol (paclitaxel) remains a cornerstone of ovarian cancer treatment. To tackle drug resistance and toxicity, second-generation targeted anti-mitotic agents and combination strategies are being explored but have yet to demonstrate meaningful clinical benefits. A limitation is the lack of a platform to compare strategies in models that capture disease heterogeneity. To overcome this, we screen 83 patient-derived ex vivo ovarian cancer models that exhibit extensive intra- and inter-patient heterogeneity, testing four distinct approaches to enhance taxol sensitivity. Inhibitors of the HSET kinesin or the Mps1 spindle assembly checkpoint kinase show minimal impact on the taxol sensitivity landscape. By contrast, Bcl-xL inhibition exerts a global anti-proliferative effect

SUBMITTER: Tighe A 

PROVIDER: S-EPMC12208324 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature