Endometriosis is typically treated as a single condition, yet patients often experience very different outcomes with the same therapy.
A new preprint from Paris-based biotech company endogene.bio, Beyond one-size-fits-all: single-cell transcriptomic signatures predict drug efficacy and reveal responder subgroups in endometriosis, suggests that this variability reflects a fundamental biological reality: endometriosis is molecularly heterogeneous across patients, lesion sites, and cell types.
This molecular heterogeneity has important implications for how endometriosis treatments are studied and developed. Treating the disease as a single entity may help explain why many clinical trials yield mixed results or fail, while matching patients to therapies based on biology could improve trial success and efficiency.
To address this heterogeneity, the researchers combined single-cell RNA sequencing – which measures gene activity in individual cells – with a computational drug-response framework. The approach focuses on the specific cell populations most likely to drive lesion persistence, rather than averaging signals across an entire tissue.
For single-cell datasets spanning eutopic endometrium and endometriotic lesions, the analysis identifies disease-associated molecular mechanisms concentrated in stromal, endothelial, and stem-like cell populations, which consistently showed disease-associated transcriptional changes linked to lesion maintenance. The model then predicts which therapeutic mechanisms may be most likely to counter these disease states and identifies responder subgroups, suggesting that a drug effective for one subset of patients may be less relevant for another.
Dr Cristina Fernández Molina, co-founder and Head of Science at endogene.bio, commented: “Endometriosis is currently classified based on symptoms and anatomical or surgical features, but these approaches don’t capture the biological programs active inside the tissue. Our work shows that what looks like unpredictable variability between patients actually reflects recurring cellular states that shape how the disease behaves and responds to treatment. This creates an opportunity to move toward more biologically informed patient stratification in research and clinical trials.”
For decades, endometriosis has been approached much like breast cancer once was – treated as a single, uniform disease rather than a spectrum of biologically distinct subtypes. In oncology, recognizing HER2-positive, hormone-receptor-positive, and triple-negative breast cancers as fundamentally different diseases transformed both patient outcomes and clinical trial design. The emerging molecular picture of endometriosis points to a similar need for precision.
The findings add to a growing body of evidence that endometriosis is not one disorder but many, each driven by distinct cellular programs and therapeutic vulnerabilities. This shift suggests that cli