Endometriosis is traditionally defined as the presence of endometrium-like tissue outside the uterus. While clinically precise, this definition obscures the reality of a disorder that is far more complex than ectopic tissue alone. Endometriosis is now understood as a chronic, multisystem, neuro-inflammatory disease — one that disrupts immune, endocrine, and nervous system function and manifests through pain, fatigue, infertility, and profound reductions in quality of life.
Despite affecting an estimated six to 10 percent of women of reproductive age — roughly 190 million people worldwide — endometriosis remains both under-recognized and under-diagnosed, with many women waiting nearly a decade before receiving a diagnosis.
The biggest challenge is that diagnosis still relies on indirect or late-stage signals. Symptoms are important, but they’re non-specific and vary widely between patients.
—María Teresa Pérez Zaballos, Endogene Bio
“The biggest challenge is that diagnosis still relies on indirect or late-stage signals,” María Teresa Pérez Zaballos, CEO of Endogene Bio, told DDN. “Symptoms are important, but they’re non-specific and vary widely between patients. Imaging is very good for certain phenotypes like deep infiltrating disease or ovarian endometriomas, but it has limited sensitivity for superficial disease and early-stage lesions that may still cause a lot of pain. And the last option, surgery, is invasive and not scalable or affordable for a condition this common.”
On top of a difficult and time-consuming diagnosis, current treatment options are not curative and only offer limited relief for many patients. Surgical excision and hormonal therapies can reduce symptoms, but efficacy is variable, recurrence is common, and side effects can be significant. Hormonal approaches are also incompatible with pregnancy, leaving women who wish to conceive with few viable options.
These gaps reflect a fundamental mismatch between the biological complexity of endometriosis and the simplicity or absence of the tools used to diagnose and treat it. Addressing this disconnect will require a shift toward earlier detection, non-hormonal therapies, and a deeper understanding of the molecular and phenotypic subtypes that define the disease — an evolution that is only now beginning to take shape.
Not a single disease
After decades of limited progress, endometriosis research is beginning to change — driven by a reframing of the disease itself. Rather than viewing endometriosis solely as misplaced uterine tissue, researchers increasingly describe it as a systemic, neuro-inflammatory condition with distinct molecular and cellular subtypes.
A recent preprint by Paris-based biotech company Endogene Bio illustrates how this reframing is beginning to move from concept to application. Using single-cell RNA sequencing combined with computational drug-response modeling, the researchers showed that the wide variability seen across endometriosis patients is not random but rooted in distinct cellular programs that shape how lesions persist and respond to treatment.
These programs were concentrated in stromal, endothelial, and stem-like cells within endometriotic lesions, which collectively showed selective sensitivity to two non-hormonal drug classes: histone deacetylase (HDAC) inhibitors and tubulin polymerisation inhibitors. Predicted drug responses, however, varied markedly across patients and anatomical sites.
Drug sensitivity could be partly explained by cellular activity. Lesions dominated by highly active stromal cells — engaged in tissue remodeling, fibrosis, and proliferation — were predicted to respond more strongly, while non-responders exhibited a more quiescent cellular state. In effect, the drugs appeared to target the most biologically active forms of the disease rather than endometriosis as a single entity.
Crucially, the molecular signatures linked to drug response in surgically obtained lesions were also detectable in eutopic endometrial stromal cells, which are naturally shed during menstruation. This raises the possibility that treatment response could one day be predicted and monitored using accessible tissue such as menstrual blood, rather than repeated surgery.
Together with an earlier preprint demonstrating the potential of menstrual-blood-derived methylation signatures as a non-invasive diagnostic tool, the findings point to a broader shift in how endometriosis could be understood, studied, and managed — suggesting that both diagnosis and treatment could be guided by molecular signals captured using non-invasive samples.
“We use menstrual blood to access uterine biology non-invasively,” said Pérez Zaballos. “We generate deep epigenetic profiles and integrate them with computational models to capture patient heterogeneity. So instead of asking only whether disease is visible, we ask what biology is present — just like we do in oncology — and that enables earlier, more informative diagnosis and treatments down the line.”
New tools
At the same time, advances in tissue engineering and patient-derived models are allowing researchers to study endometriosis in ways that better reflect its complexity in vivo. 3D organoids and whole-tissue platforms preserve the immune, stromal, and extracellular matrix interactions that are largely lost in traditional cell culture, enabling more accurate interrogation of disease mechanisms and drug response.
One of the most promising applications of this approach comes from GynQura Therapeutics, a pre-incorporation start-up based in Denmark and Belgium, that is using patient-derived organoids to model endometriosis in three dimensions. The company has built a biobank of tissue biopsies from more than 200 patients and has generated over 60 organoid lines spanning a broad spectrum of endometrial pathologies.
“Progress in understanding and treating endometriosis is hindered by poor preclinical models. Rodents do not develop the disease spontaneously since they do not menstruate, and in vitro studies rely on immortalized 2D cell lines that lack patient-specific traits,” Maj Hedtjärn, cofounder and Entrepreneur in Residence of GynQura, told DDN.
Their endometriosis-derived organoids reproduce disease-associated traits and can be expanded over many rounds of growth without losing these features. The organoids not only mirror the pathobiology of the original lesions but also have the potential to reveal patient-specific drug responses, making them a powerful tool for identifying and validating new therapeutic targets.
“Our patient-derived organoids provide a unique opportunity to study disease mechanisms, identify and validate therapeutic targets, and test novel drug candidates in a model that closely mimics the endometriotic lesions, and which captures differences between individual patients,” said Hedtjärn.
Cyclana Bio, a biotech start-up based in the UK, is bringing a complementary yet distinct approach to endometriosis research by focusing on the role of the extracellular matrix (ECM). Their research suggests that ECM dysregulation may drive inflammation and lesion persistence, meaning that therapies targeting cell–ECM interactions could address a root cause of disease.
“In conditions like endometriosis, the ECM is profoundly dysregulated and can propagate the disease,” said Léa Wenger, CEO and cofounder of Cyclana Bio. “We are gathering first-in-class ECM data from patients, building disease models of the ECM in the lab to better understand the drivers of disease, and developing therapeutics based on that understanding.”
With £5 million in pre-seed funding, Cyclana is developing whole-tissue models using menstrual fluid and lab-based systems, combined with AI-driven multi-scale data integration, to identify early biomarkers and druggable targets. This approach could potentially unlock new therapeutic pathways for endometriosis and other chronic inflammatory conditions with similar tissue-level mechanisms.
Making women’s health a priority
The emerging research and biotech activity in endometriosis signal a shift from treating symptoms to understanding —and targeting — the underlying biology. For decades, patients with endometriosis have been constrained by limited research funding, invasive diagnosis, and few effective treatment options. This new wave of investment, however, is beginning to change that story.
Companies such as Endogene Bio, GynQura Therapeutics, and Cyclana Bio illustrate how scientific advances are moving into practical application. By combining patient-derived models, multi-scale data integration, and drug-response modelling, they are pushing toward a future where endometriosis care is personalized, less invasive, and more effective.
If this momentum continues, endometriosis may finally be understood not as a mysterious condition to be managed, but as a treatable disease with measurable pathways and predictable outcomes — opening the door to a new standard of care for millions of women worldwide.
