Endometrial Cancer

P1/2, N=19, Completed, Tasly Pharmaceutical Group Co., Ltd | Recruiting --> Completed | N=132 --> 19 | Trial completion date: Dec 2027 --> Dec 2025 | Trial primary completion date: Dec 2026 --> Jun 2025

P1/2, N=78, Not yet recruiting, University College Dublin

The mutational patterns affecting homologous recombination repair differ across gynecologic and breast cancers. Further research into cancer-specific HRD mechanisms is warranted.

Advanced FIGO stage, larger tumor size, elevated PIV and CRP, and reduced albumin are key predictors of recurrence. Combining these factors provides a strong model for individualized postoperative surveillance.

Screening of a compound library using this probe identified four natural products, namely Ginkgetin, Silibinin, Ledebouriellol, and Antcin C (R), as potent UGT1A8 inhibitors. Collectively, these findings position UPro1A8 as a robust molecular tool for advancing UGT1A8 functional studies.

Molecular classification is prognostically essential in endometrial carcinoma. The integrated FIGO 2023 m system appears to enhance risk stratification relative to FIGO 2009 and non-molecular FIGO 2023. Formal comparison of staging systems is needed to confirm this improvement.

In EC cells with pre-existing MLH1 promoter methylation, MLH1-KD leads to MSI-H, enhances genomic instability, disrupts Wnt signaling, impairs cellular functions, and inhibits tumor growth, highlighting Wnt signaling and MSI-H as potential therapeutic targets in EC.

However, the predominance of the serous component showing diffuse WT1 expression is unusual for this entity and raises the possibility that the tumor represents SBT with mucinous differentiation, a potential borderline malignant counterpart of LGSC with mucinous differentiation. This case suggests a potential diagnostic overlap between SMBT and SBT, underscoring the need for further accumulation of similar cases and integrated analyses to clarify whether such tumors may warrant distinction from typical SMBT.

The results of this real-world study demonstrate that endometrial cancer is a complex disease, characterized by substantial molecular heterogeneity and varying biomarker distributions across histology, stages, and molecular subtypes. This real-world study supports the integration of comprehensive molecular profiling into routine practice to refine prognostic stratification and guide biomarker-driven therapies.

Given that our cases were identified in a relatively short time period, it is likely that GLI1-rearranged tumours are more common in the female genital tract than is realised and a high index of suspicion is required to initiate appropriate testing and establish the diagnosis. In the absence of readily available appropriate molecular testing, GLI1 immunohistochemistry can serve as an acceptably accurate surrogate biomarker for GLI1 rearrangement, since we found that GLI1 immunohistochemistry showed strong, diffuse nuclear staining in 6 GLI1-rearranged gynaecologic tumours stained for this study, whereas this was consistently negative, or at most weak/focal, in an array of 135 morphologic mimics.

The maximum tolerated dose was not reached with ifinatamab deruxtecan; however, one death due to treatment-related interstitial lung disease highlights the importance of prompt evaluation and careful management of patients who develop interstitial lung disease. Promising antitumour activity was observed across various solid tumours. These findings support further evaluation of ifinatamab deruxtecan in randomised controlled trials.

Pathway analysis revealed predominant WNT/β-catenin signaling in EBTs versus RAS-MEK-ERK pathway alterations in SMBTs resembling the seromucinous variant of ovarian endometrioid carcinoma, with additional involvement of PI3K-PTEN-AKT-mTOR and SWI/SNF chromatin remodeling pathways in both. These findings demonstrate that EBTs and SMBTs possess distinct morphologic and molecular profiles, expanding the molecular characterization of early ovarian endometrioid-type neoplasms.