PRECISE · Predictive Evaluation of Chemotherapy Resistance by Innovative Single-molecule Chromatin Signature Examination

Chemotherapy resistance remains a major obstacle in cancer treatment. In ovarian cancer, up to 50% of patients treated with platinum-based chemotherapy fail to respond yet still experience severe toxicity and disease progression. Biomarkers, like homologous recombination deficiency scores, offer only partial predictive power because resistance often develops through adaptive mechanisms, including replication stress tolerance, secondary mutations, and DNA repair reprogramming, which static genetic tests cannot capture. There is an urgent clinical and market need for a functional diagnostic tool that can reliably predict therapy response early, by directly measuring therapy-specific effects in patient-tumor cells before treatment.We have developed ChromStretch (CS), a patented single-molecule chromatin fiber assay that visualizes tumor cells response to replication stress induced by chemotherapy. By stretching chromatin fibers from patient-derived cells, CS detects drug-induced changes in two key biomarkers at sites of DNA replication, providing a direct functional readout of resistance potential. The test requires only a very small number of cells and delivers results within ~72 hours from fresh or liquid biopsy. Pilot experiments showed that CS predictions correlate with clinical outcomes, highlighting strong feasibility and translational potential.The PRECISE project will validate CS in a prospective study of ovarian cancer patients. Objectives are to:(i)assess reproducibility and robustness across clinical samples;(ii)define biomarker positivity thresholds;(iii)correlate assay results with response and survival outcomes;(iv)explore valorization pathways, including prototype-kit development & early engagement with industrial partners.Successful completion will provide proof-of-concept for CS as a rapid, minimally invasive diagnostic to improve patient stratification, avoid ineffective treatments, & enable more personalized strategies in ovarian and other cancers.