endometrial cancer

Overview

Endometrial cancer (EC) is a malignant neoplasm originating from the epithelial lining of the uterus (the endometrium) and represents one of the most prevalent gynecological malignancies worldwide. It is classified into distinct molecular subtypes — including mismatch repair deficient (dMMR), microsatellite instable (MSI-H), and mismatch repair proficient (MMRp/MSS) tumors — each with different prognostic implications and therapeutic vulnerabilities. The disease is highly heterogeneous at both the genomic and histological levels, with hormone-dependent subtypes relying on nuclear hormone receptors, particularly progesterone and estrogen receptors, to sustain lineage identity and proliferative signaling. Risk factors include obesity, diabetes, hypertension, and prolonged unopposed estrogen exposure. Early-stage disease typically presents with abnormal uterine bleeding and carries a favorable prognosis, while advanced or recurrent disease remains therapeutically challenging, with limited durable treatment options historically available.

The molecular landscape of endometrial cancer is shaped by alterations in DNA mismatch repair pathways, oncogenic driver mutations, and epigenetic modifications such as MLH1 promoter methylation — a mechanism capable of inducing dMMR status even in the absence of germline mutations. The disease shares biological and clinical intersections with ovarian cancer, including the phenomenon of synchronous primary tumors of the female genital tract, which must be carefully distinguished from metastatic spread. Emerging research has highlighted the role of biomarkers such as cytochrome b561 (CYB561), lineage plasticity driven by nuclear hormone receptor signaling, and immune checkpoint pathways in shaping tumor behavior and response to therapy. These insights are fueling a new era of precision oncology for endometrial cancer, integrating immunotherapy, targeted agents, and epigenetic diagnostics.

Focus of Latest Publications

Recent research on endometrial cancer spans therapeutic innovation, surgical optimization, molecular characterization, and diagnostic advancement, reflecting the disease's growing complexity and clinical urgency.

immunotherapy and Targeted Therapy

A notable case report (PMID: 42077092) described the use of anlotinib — a multi-target tyrosine kinase inhibitor — combined with envafolimab, an anti-PD-L1 checkpoint inhibitor, as neoadjuvant therapy in a patient with chemotherapy-refractory advanced endometrial cancer who also presented with early-stage lung cancer. This case highlighted the potential for combination immunotherapy strategies in refractory settings where standard chemotherapy has failed.

The phase 3 DUO-E/GOG-3041/ENGOT-EN10 trial (PMID: 41690202; PMID: 41943281) demonstrated statistically significant progression-free survival benefit with carboplatin and paclitaxel chemotherapy combined with durvalumab (an anti-PD-L1 agent), followed by durvalumab with or without olaparib (a PARP1 inhibitor) maintenance, compared to carboplatin/paclitaxel alone in patients with advanced or recurrent endometrial cancer. Exploratory analyses focused specifically on biomarker heterogeneity within the MMR-proficient subgroup, underscoring the need for refined patient stratification. A plain-language summary of the DUO-E results (PMID: 41943281) further contextualized these findings within the broader landscape of limited treatment options for newly diagnosed advanced or recurrent disease.

Immune checkpoint inhibitor-related toxicity was examined in a real-world cohort study (PMID: 42012269), which reported that patients who developed hyperthyroidism as an immune-related adverse event were significantly more likely to have renal cell carcinoma or endometrial cancer compared to those with liver cancer or bladder cancer, suggesting tumor-type-specific immune profiles that may modulate adverse event risk.

Surgical Approaches

Sentinel lymph node (SLN) mapping using indocyanine green (ICG) was evaluated in a study comparing conventional laparoscopy versus robot-assisted surgery in apparent early-stage endometrial cancer (PMID: 42157366), with the aim of determining whether the minimally invasive platform influences SLN detection outcomes. In a parallel investigation, the influence of robotic-assisted systems on hysterectomy outcomes for both benign and Malignant Disease — including endometrial carcinoma requiring pelvic lymph node dissection — demonstrated that robotic surgery significantly reduced operative time by approximately 48.5 minutes compared to conventional approaches (PMID: 42115535).

Molecular and Epigenetic Characterization

A case report focusing on MLH1 promoter methylation-induced dMMR/MSS endometrial cancer (PMID: 42001360) illuminated the epigenetic basis by which tumors can acquire mismatch repair deficiency without germline alterations, with important implications for immunotherapy eligibility. The expression of CYB561 in endometrial carcinoma tissues was investigated (PMID: 42082769) to determine its relationship with clinicopathological characteristics and patient prognosis, adding to the growing catalog of tissue-based biomarkers in EC.

Fertility-preserving treatment with progestin was studied in the context of molecular classification (PMID: 42068048), with findings indicating that molecular subtype significantly influences treatment outcomes in patients with endometrial carcinoma and atypical endometrial hyperplasia — providing a rationale for integrating molecular profiling into fertility-sparing decision-making.

Diagnostics and Liquid Biopsy

The cervico-vaginal DNA methylation WID-qEC test was validated as an epigenetic diagnostic tool capable of accurately detecting endometrial and cervical cancers using non-invasive cervico-vaginal samples (PMID: 41609407). Notably, the test was also associated with ovarian cancer detection in the absence of endometrial and cervical cancer, demonstrating cross-cancer diagnostic utility.

Broader Biological Insights

Endometrial carcinoma was identified alongside breast cancer and prostate cancer as hormone-dependent cancers in which nuclear hormone receptor signaling sustains lineage identity and growth, with lineage plasticity emerging as a mechanism of treatment resistance (PMID: 42014520). ovarian cancer and endometrial cancer were jointly characterized as highly heterogeneous gynecological malignancies with distinct molecular subtypes, therapeutic responses, and clinical outcomes, with radiogenomics approaches proposed as a framework to unravel this heterogeneity (PMID: 41192450). The use of peptide-based immunotargeting — including peptide-drug conjugates — was highlighted as a precision medicine strategy for improving both the efficacy and safety of treatments for uterine and ovarian cancers (PMID: 41930712). Synchronous endometrial and ovarian cancers were discussed as a distinct diagnostic challenge requiring differentiation from metastatic disease (PMID: 42215058).

Key Publications

• Jun Histological evaluation of hysterectomy specimens after NovaSure® endometrial ablation in patients with atypical endometrial hyperplasia or endometrial carcinoma. (Archives of gynecology and obstetrics, 2026, PMID 42315802): "This analysis addresses the rare but clinically relevant situation in which endometrial carcinoma (EC) or atypical hyperplasia (AEH) is identified histologically after endometrial ablation in premenopausal patients."
• Jun Artificial intelligence-driven integration of multi-biofluid omics and clinical phenotype enables stratification of endometrial cancer. (Cell reports. Medicine, 2026, PMID 42140194): "Endometrial cancer (EC) incidence is rising, yet current diagnostics lack precision and scalability."
• Jun Multi-omics analysis positions DNA2 at the interface of genome integrity programs and tumor behavior in pan-cancer. (Functional & integrative genomics, 2026, PMID 42307783): "In endometrial cancer, the highest frequency of genetic changes (~ 7%) was observed."
• Jun Risk-Based Survival Outcomes in Early-Stage Endometrial Cancer: Impact of Radiation Therapy. (Journal of Korean medical science, 2026, PMID 42299140): "Although a new paradigm incorporating molecular and histological classifications has emerged, molecular classification is not routinely performed for all patients in real-world practice."
• May Exploring synchronous endometrial and ovarian cancers. (BMJ case reports, 2026, PMID 42215058): "Synchronous tumours of the female genital tract need to be distinguished from metastatic s such as primary ovarian or endometrial cancer with metastasis to the other site."
• May Sentinel Lymph Node Mapping with Indocyanine Green in Endometrial Cancer: Does the Minimally Invasive Platform Matter? (Journal of investigative surgery : the official journal of the Academy of Surgical Research, 2026, PMID 42157366): "To compare indocyanine green (ICG) sentinel lymph node (SLN) mapping between conventional laparoscopy and robot-assisted surgery in apparent early-stage endometrial cancer."
• May The cervico-vaginal DNA methylation WID-qEC test: An epigenetic marker associated with ovarian cancer in the absence of endometrial and cervical cancer. (International journal of cancer, 2026, PMID 41609407): "The DNA methylation-based WID-qEC test, applied to cervico-vaginal samples, has been validated for the accurate detection of endometrial and cervical cancers."
• May The influence of robotic-assisted systems on the surgical approach and outcomes in hysterectomy for benign and malignant diseases. (Journal of robotic surgery, 2026, PMID 42115535): "However, for endometrial carcinoma with pelvic lymph node dissection, robotic surgery reduced operative time by 48.5 min (P < 0.05)."
• May Expression and clinical significance of cytochrome b561 in endometrial cancer. (Journal of cancer research and clinical oncology, 2026, PMID 42082769): "To investigate the expression level of cytochrome b561 (CYB561) in endometrial carcinoma tissues and analyze its relationship with clinicopathological characteristics and patient prognosis."
• May Anlotinib plus envafolimab as neoadjuvant therapy in a patient with chemotherapy-refractory advanced endometrial cancer: A case report. (Human vaccines & immunotherapeutics, 2026, PMID 42077092): "advanced endometrial cancer and early-stage lung cancer."