Single-Cell Profiling Reveals Chemotherapy Resistance Signals in Ovarian Cancer

It often causes few symptoms, leading to diagnosis at an advanced stage, and has a five-year survival rate below 40%. Treatment is further complicated by chemotherapy resistance, which may reflect differences in tumor cell behavior that DNA mutations alone cannot explain. New findings suggest that single-cell profiling at diagnosis can capture these differences and identify tumor characteristics associated with treatment failure.

One Biosciences (Paris, France), working with the French National Centre for Scientific Research, Institut Curie, and Sorbonne Université, found that some ovarian cancer cells may be epigenetically primed to resist cytotoxic chemotherapy. The work used clinical-grade single-cell profiling to examine high-grade serous ovarian tumors. One Biosciences has developed OneMap, an end-to-end molecular profiling platform designed to characterize tumors at single-cell resolution.

By analyzing single-cell RNA profiles from tumor samples collected before and after chemotherapy, the researchers tracked cellular changes associated with resistance. These analyses showed that DNA mutations alone could not explain the observed changes, highlighting the importance of examining tumor cell states alongside genetic alterations.

Tumors with a higher baseline prevalence of cellular states linked to chemotherapy resistance were associated with poorer overall survival. The team also identified epigenetic markers associated with resistance to the chemotherapy agents evaluated. The profiling technology can be applied to standard formalin-fixed, paraffin-embedded biopsy samples, making it compatible with tissue routinely collected in clinical care.

The full study was published online in Cancer Discovery on October 19, 2026. The findings indicate that initial tumor composition can predict overall survival in high grade serous ovarian cancer. The investigators also stated that clinical-grade single-cell profiling may help identify and track mechanisms of resistance across multiple cancer types.

“Ovarian cancer tumors are very diverse, with many different cell types. These cells can do many different things, some of which help the tumor resist chemotherapy. In this study we identified all the functional states present in a tumor both before and after treatment and found that a patient’s initial tumor profile predicted their outcome. By using single-cell profiling to identify functional states associated with chemotherapy resistance, we may be better able to predict who will respond to therapy and who won’t, giving physicians an opportunity for more personalized treatment strategies,” said Céline Vallot, Ph.D., co-founder and chief scientific officer at One Biosciences.

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