Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Endometrial Carcinoma. Core disease mechanisms, molecular and cellular pat...

This report is retrieval-only and is generated directly from Asta results.

• Papers retrieved: 20
• Snippets retrieved: 20

Relevant Papers

[1] CELL MOTILITY PROTEINS IN ENDOMETRIUM CARCINOMA AND ENDOMETRIAL HYPERPLASIA: ASSOCIATION WITH CANCER RISK

• Authors: N. Yunusova, L. Spirina, A. Chernyshova, E. Kolegova, E. Sidenko et al.
• Year: 2020
• Venue: Siberian journal of oncology
• URL: https://www.semanticscholar.org/paper/a53b54227e6d96f08544d59d592d357bace1c458
• DOI: 10.21294/1814-4861-2020-19-5-51-60
• Summary: The level of actin-binding proteins as well as the total calpain activity were enhanced in endometrium carcinoma tissues compared to endometrial hyperplasia, suggesting that levels of thymosin β-4, cofilin and total calPain activity are independent cancer risk factors in patients with endometrioid EC and may be considered as predictive biomarkers.
• Evidence snippets:
• Snippet 1 (score: 0.504) > Endometrium carcinomas (EC) are the most common gynecological malignancy worldwide, which are connected with considerable mortality [1]. The endometrioid adenocarcinoma is the most frequent histological variant, accounting for about 80 % of the disease cases. Risk factors for EC include age, obesity, menstrual, reproductive and lifestyle factors [2]. Hormonal and metabolic mechanisms are particularly strongly implicated in the pathogenesis of endometrioid adenocarcinoma [2][3][4]. This subtype is often preceded by precursor lesions, atypical endometrial hyperplasia [5]. Complex hyperplasia and atypical hyperplasia, in particular, are more likely progressed to cancer and therefore are commonly treated with a progestin or hysterectomy [6]. > Among the factors that may influence the inception and course of EC estrogens, components of signaling pathways, proteases, growth and transcriptional factors have been most intensively studied [7][8][9][10]. However, molecular mechanisms involved in EC development are not fully understood. Neoplastic cancer transformation and following cancer progression are associated with the basic cancer properties as disorders of the cell adhesion and locomotion. The acquirement of the malignant phenotype leads to changes in cell cytoskeleton, wich are important for epithelial cancer cell proliferation, migration and epithelialmesenchymal transition [11]. The remodeling of actin cytoskeleton plays a central role in generating force to drive cell locomotion, and the cytoskeleton remodeling is regulated by a plethora of actin-binding proteins (ABPs).

[2] Endometriosis-associated Ovarian Clear Cell Carcinoma: A Special Entity?

• Authors: Yue Sun, Guoyan Liu
• Year: 2021
• Venue: Journal of Cancer
• URL: https://www.semanticscholar.org/paper/336750a5dee5ca2548c46099dda9b7c9d9148fda
• DOI: 10.7150/jca.61107
• PMID: 34659566
• PMCID: 8518018
• Citations: 33
• Influential citations: 4
• Summary: To improve the survival of OCCC patients, it is necessary to better understand its specific carcinogenic mechanism and explore new treatment strategy, including molecular target.
• Evidence snippets:
• Snippet 1 (score: 0.502) > Endometriosis is an estrogen-dependent disease, which serves as a precursor of ovarian cancer, especially clear cell carcinoma (OCCC) and endometrial carcinoma. Although micro-environmental factors such as oxidative stress, immune cell dysfunction, inflammation, steroid hormones, and stem cells required for malignant transformation have been found in endometriosis, the exact carcinogenic mechanism remains unclear. Recent research suggest that many putative driver genes and aberrant pathways including ARID1A mutations, PIK3CA mutations, MET activation, HNF-1β activation, and miRNAs dysfunction, play crucial roles in the malignant transformation of endometriosis to OCCC. The clinical features of OCCC are different from other histological types. Patients usually present with a large, unilateral pelvic mass, and occasionally have thromboembolic vascular complications. OCCC patients are easier to be resistant to chemotherapy, have a worse prognosis, and are usually difficult to treat. To improve the survival of OCCC patients, it is necessary to better understand its specific carcinogenic mechanism and explore new treatment strategy, including molecular target.

[3] Mechanisms of Cisplatin in Combination with Repurposed Drugs against Human Endometrial Carcinoma Cells

• Authors: Chi-Kang Lin, Shu‐Ting Liu, Zih-Syuan Wu, Yu‐Chi Wang, Shih-Ming Huang
• Year: 2021
• Venue: Life
• URL: https://www.semanticscholar.org/paper/58599163adcb82fa2f4f0fe4290cbc2a8900e814
• DOI: 10.3390/life11020160
• PMID: 33669781
• PMCID: 7922822
• Citations: 13
• Summary: Three human endometrial cancer cell lines were used to investigate the responsiveness of cisplatin alone and in combination with potential repurposed drugs and potential strategies for enhancing the efficacy of cis platin to overcome drug resistance inendometrial carcinoma patients are suggested.
• Evidence snippets:
• Snippet 1 (score: 0.476) > Type I tumors also show microsatellite instability and PTEN (Phosphatase and Tensin Homology) mutations. PTEN is a tumor suppressor gene that negatively regulates the PI3K/AKT (Phosphatidylinosito 3-kinase/a serine/threonine protein kinase) signaling pathway, mutations within which contribute to the pathogenesis of endometrial carcinoma. Type II tumors exhibit p53 mutations and chromosomal instability [7]. p53 mutations are predictive of prognosis in endometrial cancer and are associated with unfavorable outcomes [8]. Considering all the various genes and signaling pathways potentially involved in the pathogenesis of endometrial cancer, strategies for targeting them would seem to be a reasonable therapeutic approach. > The primary cause of death from endometrial cancer is disease recurrence, leading to progressive growth of the tumor [9]. Although chemotherapy or radiotherapy can target most tumor cells, relapse occurs in many cases because of drug resistance. Cisplatin is a well-known chemotherapeutic drug that acts by crosslinking with the N 7 of guanine in DNA [10]. Its mode of action is related to its ability to interfere with DNA repair mechanisms, cause DNA damage, and then induce apoptosis in cancer cells [11]. In recent years, much research has focused on the role of oxidative stress, defined as an imbalance between reactive oxygen species (ROS) and antioxidants, in the pathophysiology of malignant transformation in endometriosis [12][13][14][15]. But oxidant/antioxidant imbalance is a double-edged sword that can promote both carcinogenesis and cancer cell death. Cisplatin induces ROS that triggers cell death [16]. On the other hand, cancer cells frequently develop resistance to cisplatin that has been attributed to three molecular mechanisms: increased DNA repair, altered cellular accumulation, and increased drug inactivation [17].

[4] Molecular Aspects of Cancer Research Endometrium – The Prospect of Personalized Treatment

• Authors: Movchan Oksana
• Year: 2021
• Venue: Journal of Pharmaceutical Research International
• URL: https://www.semanticscholar.org/paper/8be281407dffce5059e68bf795257a809ef8b2ff
• DOI: 10.9734/jpri/2021/v33i43a32496
• Citations: 1
• Summary: The effective treatment and therapy need a detailed understanding of the molecular mechanisms underlying the creation and progression of endometrial cancer, as well as the development of innovative targeted therapeutic agents.
• Evidence snippets:
• Snippet 1 (score: 0.463) > Detailed In June 2021, we conducted a search for this systematic review and meta-analysis. We included research on endometrial cancer molecular pathways and treatment outcomes. The terms molecular mechanisms, endometrial cancer, uterine cancer, treatment, and therapy were used in the search. We also looked through the reference lists of papers found during the initial search to see if there were any other studies that were relevant. Authors independently vetted titles and abstracts for inclusion. Fig. 3 depicts the search technique as well as the selection criteria. > The inclusion and exclusion criteria applied to select studies for the meta-analysis as showed in Table 1. Author name, year, drug/therapeutic agent, trial phase, median progression and medial overall survival rate, number of patients enrolled in each study, mean age of the study participants, and drugs molecular target were retrieved. Endometrial cancer is one of the most prevalent malignancies among women worldwide, with an increasing incidence and death rate in the United States [1]. Postmenopausal women, on average 60 years old when diagnosed, are the majority of those affected by this malignancy. Between the ages of 75 and 79, the largest prevalence occurs, with 85% of cases occurring after the age of 50 and only 5% occurring before the age of 40. These facts were also discovered through our meta-analysis as a total of 1049 patients enrolled in all included studies with mean age of > 60. Fig. 2 depicts some essential biological pathways involved in endometrial cancer development. All endometrial malignancies should be screened for DNA mismatch repair gene mutations, according to experts [25]. The majority of endometrial cancer patients require surgery, which involves hysterectomy, bilateral salpingo-oophorectomy, and lymph node assessment. Patients with unresectable illness or significant medical comorbidities may get nonsurgical treatment in the form of primary radiation with or without chemotherapy, or chemotherapy alone. Hormonal therapy might potentially be used to treat people who are medically inoperable but dont want surgery, radiation, or cytotoxic chemotherapy.

[5] The Molecular and Cellular Mechanisms of Endometriosis: From Basic Pathophysiology to Clinical Implications

• Authors: Heidi Mariadas, Jie-Hong Chen, Kuo-Hu Chen
• Year: 2025
• Venue: International Journal of Molecular Sciences
• URL: https://www.semanticscholar.org/paper/cf19f74bbf3d2e02ce3d22f6f8873d5667b7456f
• DOI: 10.3390/ijms26062458
• PMID: 40141102
• PMCID: 11941934
• Citations: 40
• Summary: Current therapies, such as GnRH agonists, suppress ovarian hormone production but face limitations in long-term efficacy and side effects, with emerging approaches focusing on molecular pathways, immune modulation, and hormonal regulation for more effective, personalized therapies.
• Evidence snippets:
• Snippet 1 (score: 0.449) > Endometriosis is a complex, multifactorial disorder characterized by the growth of endometrial-like tissue outside the uterine cavity. The intricacies of its molecular and cellular mechanisms highlight the challenges in fully understanding the disease and developing effective therapeutic strategies. This discussion synthesizes the primary theories of pathophysiology, cellular mechanisms, and molecular pathways involved in the disease, emphasizing the interplay of genetic, immunologic, and hormonal factors. > The pathogenesis of endometriosis involves multiple overlapping theories, none of which fully explain the heterogeneity of the disease. Retrograde menstruation, the most widely known hypothesis, provides a logical mechanism for the dissemination of endometrial cells to ectopic sites [106]. However, its inability to account for cases of endometriosis in non-menstruating individuals, males, or distant anatomical locations necessitates complementary explanations [107]. The vascular and lymphatic dissemination hypothesis further supports the notion of systemic spread, while the coelomic metaplasia theory extends the understanding of ectopic lesion formation, particularly in patients with Müllerian anomalies or postmenopausal women [108]. Genetic and epigenetic influences are emerging as crucial contributors to disease susceptibility and progression, highlighting the role of heritable factors and acquired molecular modifications in shaping cellular behaviors [109]. > Endometrial stem cells and progenitors, such as eMSCs and eEPs, are critical in the establishment of endometriotic lesions. Their unique capacity for adhesion, proliferation, and differentiation in ectopic environments distinguishes them as central players in disease progression [113]. The altered integrin and cadherin profiles in these cells enhance their ability to adhere to peritoneal surfaces, while the influence of the inflammatory microenvironment further supports their survival and growth. Notably, ESCs and SMCs contribute to lesion heterogeneity, with their potential origins spanning basal endometrial layers and reactivated coelomic epithelium [119]. Understanding the lineage and differentiation of these cells remains a critical area of research, with implications for diagnostic and therapeutic approaches.

[6] Systematic Analysis of Endometrial Cancer-Associated Hub Proteins Based on Text Mining

• Authors: Huiqiao Gao, Zhenyu Zhang
• Year: 2015
• Venue: BioMed Research International
• URL: https://www.semanticscholar.org/paper/8e1224bf31c98e1192ebed7cd7a17547e55fd171
• DOI: 10.1155/2015/615825
• PMID: 26366417
• PMCID: 4561104
• Citations: 9
• Summary: The authors' data may help to reveal the molecular mechanisms of EC development and provide implications for targeted therapy for EC, however, corrections between certain proteins and EC continue to require additional exploration.
• Evidence snippets:
• Snippet 1 (score: 0.449) > Endometrial cancer is one of the most common gynecologic malignancies, and the incidence of this cancer continues to increase [1]. During the prior several decades, progress in molecular biology has improved our understanding of the occurrence and development of EC. It has been established that the biological behavior of tumors is controlled by functional proteins within cells and the signaling pathways in which these proteins are involved. Therefore, studies on the structure and function of hub proteins in signaling pathways may be valuable for diagnosing EC and for determining targeted therapies for this disease. To date, research has examined a large number of EC-related genes and proteins that could potentially be used as biomarkers or targets for diagnosis or treatment [2,3]. However, most published papers regarding EC have focused on only a handful of genes and proteins. Although the research objectives of molecular biology are shifting from single genes or proteins to genomics or proteomics, there are a limited number of systematic studies of whole-genome expression in the context of EC. > At present, text mining (TM) technology is widely used in biomedical research to extract information from large quantities of biomedical literature and construct databases of disease-related genes, proteins, and molecular interactions [4,5]. In this study, we systematically characterized the expression of EC-associated genes by mining data from the PubMed document retrieval system. In addition, we used bioinformatics methods to analyze the functions, pathways, and networks of relevant hub proteins.

[7] Genetic profiling and pathway analysis in bladder carcinoma: Implications for therapeutic targeting

• Authors: Sampara Vasishta, U. Adiga, Alfred J Augustine
• Year: 2025
• Venue: Turkish Journal of Surgery
• URL: https://www.semanticscholar.org/paper/405be9f362a5373a199f2dab695c9f0bf33d4e85
• DOI: 10.47717/turkjsurg.2025.2025-3-33
• PMID: 40726145
• PMCID: 12687403
• Summary: Comprehensive insights into the molecular underpinnings of bladder carcinoma are provided, highlighting interconnected pathways and potential therapeutic targets that could be exploited for therapeutic intervention.
• Evidence snippets:
• Snippet 1 (score: 0.447) > Objective Bladder carcinoma represents a significant challenge in oncology due to its heterogeneous molecular nature. This study aimed to identify key genetic factors and molecular pathways involved in bladder carcinoma pathogenesis to facilitate the development of targeted therapies. Material and Methods The top 30 genes associated with bladder carcinoma were retrieved from the disease gene network database. Comprehensive bioinformatic analysis was performed using various enrichment tools, including gene ontology biological process, cellular component, molecular function analyses, and pathway mapping through WikiPathways and metabolite associations through human metabolome database. Drug interactions were evaluated using DrugMatrix data. Results Gene ontology analysis revealed significant enrichment of cancer-related biological processes, cellular components, and molecular functions. Pathway analysis identified strong associations with head and neck squamous cell carcinoma, cancer pathways, pleural mesothelioma, endometrial cancer, and bladder cancer pathways. Key genes including CDKN2A, PTEN, EGFR, PIK3CA, HRAS, FGFR3, and TP53 were implicated across multiple pathways. Metabolite analysis showed significant associations with phosphatidylinositol derivatives, highlighting the importance of the PI3K pathway. Drug interaction analysis revealed potential modulatory effects of several compounds including sertraline, valproic acid, and hydroxyurea on gene expression patterns in bladder carcinoma. Conclusion This study provides comprehensive insights into the molecular underpinnings of bladder carcinoma, highlighting interconnected pathways and potential therapeutic targets. The significant overlap with other cancer types suggests common oncogenic mechanisms that could be exploited for therapeutic intervention. Further validation of these findings in clinical samples may facilitate the development of personalized treatment approaches for bladder carcinoma patients.

[8] Exploring Bioinformatics Tools to Analyze the Role of CDC6 in the Progression of Polycystic Ovary Syndrome to Endometrial Cancer by Promoting Immune Infiltration

• Authors: Yuh-Min Song, Jing Zhang, Yaohui Li, Lufeng Cheng, Huaying Song et al.
• Year: 2024
• Venue: International Journal of Molecular Sciences
• URL: https://www.semanticscholar.org/paper/444a9cee2be864d73f3f494e70951b20db3a32a2
• DOI: 10.3390/ijms252312974
• PMID: 39684684
• PMCID: 11640967
• Citations: 2
• Summary: It is demonstrated that CDC6 regulates the progression of PCOS to EC and promotes immune infiltration and PI3K-AKT pathway via the PI3K-AKT pathway.
• Evidence snippets:
• Snippet 1 (score: 0.447) > Polycystic ovarian syndrome (PCOS) is a common reproductive endocrine disease that affects 4-10% of women of childbearing age worldwide. Its clinical symptoms include chronic anovulation, ultrasound visibility of polycystic ovary morphology, and hyperandrogenism [1]. PCOS is characterized by high heterogeneity, complex symptoms, and difficult treatment. The consequent endocrine and metabolic abnormalities can also lead to various complications and increase the risk of endometrial cancer (EC) [2]. Women with PCOS are 3-4 times more likely to develop endometrial cancer than healthy women [3]. > EC is the sixth most common malignant tumor in women, and its incidence and mortality continue to increase annually. It is estimated that the prevalence of this disease will increase by 50-100% by 2030 [4,5]. The primary clinical symptoms of EC include dysfunctional uterine bleeding, menorrhagia, menstrual irregularities, and infertility [6]. PCOS is a major risk factor for the development and progression of type I EC [7,8]. Elevated estrogen levels, hyperinsulinemia, and decreased apoptosis play key roles in the 2 of 25 occurrence [9,10]. However, the exact underlying molecular mechanism remains unclear. PCOS serum-derived exosomal miR-27a-5p stimulates EC cell migration and invasion [11]. Matà et al. [12] reported that overexpression of the PI3K/Akt signaling pathway underlies the development of endometrial hyperplasia and carcinogenesis in patients with PCOS characterized by insulin resistance (PCOS-IR). In addition, IGF1/IGFBP pathway-related genes may contribute to an increased risk of EC in women with PCOS [13]. However, the molecular mechanism underlying EC in patients with PCOS remains unclear. This has hindered effective clinical prevention and treatment. > Cell division cycle 6 (CDC6), sited on human chromosome 17q21.3, is a vital regulatory protein for the beginning of DNA copying in eukaryotic cells.

[9] Endometrial cancer: a genetic point of view

• Authors: B. Bianco, C. Barbosa, C. M. Trevisan, A. Laganà, E. Montagna
• Year: 2020
• Venue: Translational Cancer Research
• URL: https://www.semanticscholar.org/paper/437eaa43fab26f65bc61dc446928b2041611b246
• DOI: 10.21037/tcr-20-2334
• PMID: 35117373
• PMCID: 8797944
• Citations: 22
• Influential citations: 1
• Summary: The current challenge is the integration of clinicopathologic and molecular factors to improve the diagnosis, prognosis, and treatment of endometrial cancer.
• Evidence snippets:
• Snippet 1 (score: 0.444) > It has become well known in the past two decades that endometrial cancers present the highest molecular complexity among common tumor types, and its mechanistic heterogeneity is conformable with histologic and clinical variability (29). (11). > A recent characterization of 373 endometrial carcinomas using array-and sequencing-based technologies, through an integrated analysis of genomic, transcriptomic, and proteomic data by The Cancer Genome Atlas (TCGA) provided comprehensive information about pathway alterations and molecular mechanisms, describing four different molecular subgroups. Polymerase epsilon (POLE)-mutated subgroup with very high mutation rates (232×10 6 mutations/Mb) (ultramutated) is associated with good prognosis and account for 7-10% of endometrioid carcinomas. MSI subgroup with frequent hypermethylation of MLH1 promoter and elevated mutation rates (18× 10 6 mutations/Mb) account for 28-30% of endometrioid carcinomas. Low copy number alterations subgroup with low mutation rate (2.9×10 6 mutations/Mb) represents 39% of endometrioid carcinomas, and high copy number subgroup (serous-like) with low mutation rate (2.3× 10 6 mutations/Mb) but frequent TP53 mutations with worse prognosis represents serous carcinoma (94%). The candidate driver or pathogenic genes varied in all four subgroups, with 190 genes in the POLE subgroup, 21 in the MSI subgroup, 16 in the low copy number subgroup, and 8 in the high copy number subgroup (3,11,12) ( Table 2). > Endometrioid carcinomas were present in all four subgroups. Endometrioid carcinoma is generally characterized by frequent derangements of the PI3K-PTEN-AKT-mTOR, RAS-MEK-ERK, and canonical WNT-β-catenin pathways. Endometrial cancer presents more mutations than any other tumor type studied thus far in the PI3K/AKT pathway by TCGA. The PI3K-PTEN-AKT-mTOR signal transduction pathway regulates cell growth and survival, synthesis of specific proteins, and metabolism. The RAS-RAF

[10] Protein Kinase Cα Modulates Estrogen-Receptor-Dependent Transcription and Proliferation in Endometrial Cancer Cells

• Authors: Alicia M. Thorne, T. Jackson, V. Willis, A. Bradford
• Year: 2013
• Venue: Obstetrics and Gynecology International
• URL: https://www.semanticscholar.org/paper/56552b82db80db2a59b4cd462edd1a523c13f9a4
• DOI: 10.1155/2013/537479
• PMID: 23843797
• PMCID: 3703424
• Citations: 8
• Summary: It is demonstrated that expression of active, myristoylated PKCα conferred ligand-independent activation of estrogen-receptor- (ER-) dependent promoters and enhanced responses to estrogen, and evidence suggests that PKC α and estrogen signal transduction pathways functionally interact, to modulate ER-dependent growth and transcription.
• Evidence snippets:
• Snippet 1 (score: 0.441) > Endometrial cancer is the most common invasive gynecological malignancy in the United States, accounting for 45,000 new cancer cases and over 7,500 deaths annually [1]. However, molecular mechanisms underlying its etiology and pathophysiology are poorly understood. Endometrial carcinomas are derived from glandular epithelium and typically divided into two subtypes based on clinical, histological, and molecular characteristics [2,3]. Type I tumors, comprising 80% of cases, are generally well or moderately differentiated with endometrioid morphology and are associated with chronic unopposed estrogen exposure and hyperplasia. By contrast, type II tumors are more heterogeneous, poorly differentiated and may be estrogen independent, arising in a background of atrophic endometrium [2,4]. The prevalence of advanced stage, high-grade tumors, of both types, with recurrent metastatic disease is increasing [5,6]. Such cancers typically have a poorer prognosis and are refractory to current therapeutic regimens [7]. > Endometrioid tumors retain expression of estrogen (ER) and progesterone (PR) receptors [8], and estrogen is a critical regulator of endometrial proliferation [9,10]. Indeed, the majority of endometrial cancers are thought to arise due to unopposed estrogen action leading to hyperplasia and malignant transformation [2,11]. However, our understanding of the molecular mechanisms underlying the pathophysiology of endometrial cancer lags far behind that of other hormonedependent malignancies such as breast, prostate and ovarian cancer [2,8,12,13]. > The protein kinase C (PKC) family has been implicated in the regulation of numerous signal transduction pathways, modulating cell growth, differentiation, and survival [14][15][16]. In endometrial cancer cells and primary endometrial epithelium, expression of PKC is increased in response to treatment with estrogen and tamoxifen and may underlie the proliferative actions of these agents in the endometrium [17,18].

[11] lncRNA MIR210HG promotes the progression of endometrial cancer by sponging miR-337-3p/137 via the HMGA2-TGF-β/Wnt pathway

• Authors: Jian Ma, Fanfei Kong, Di Yang, Hui Yang, Cuicui Wang et al.
• Year: 2021
• Venue: Molecular Therapy. Nucleic Acids
• URL: https://www.semanticscholar.org/paper/a9d51038bbf7aef6a345ad5d616f8e7c462dae7c
• DOI: 10.1016/j.omtn.2021.04.011
• PMID: 34094710
• PMCID: 8141672
• Citations: 37
• Influential citations: 2
• Summary: The findings on the MIR210HG-miR-337-3p/137-HMGA2 axis illustrate its potential as a target for endometrial cancer therapeutic development and shows its potential to act as a molecular sponge to regulate the expression of HMGA2.
• Evidence snippets:
• Snippet 1 (score: 0.440) > Endometrial cancer is the fifth-most-common fatal malignancy among women globally and first among gynecological malignancies in Europe and the United States. 1 With improvements in social and economic conditions, the incidence of endometrial cancer has also increased, while the age of onset has decreased. 2 Metastatic or recurrent endometrial cancer is incurable in most cases, and management prolongs the patient's life and relieves symptoms. 3 With the elucidation of the molecular mechanism of endometrial cancer, drug-targeted therapies have proven efficacy. 4,5 Nonetheless, patients with advanced endometrial cancer may develop drug resistance with adverse consequences. 6 Therefore, further research on the molecular mechanism of endometrial cancer is warranted to identify potential drug targets for better clinical treatment and outcomes. > Long non-coding RNAs (lncRNAs) are involved in almost all tumorigenesis processes. 7,8 The lncRNA can be used as competing endogenous RNAs (ceRNAs) that compete with microRNA (miRNA) sponges to regulate multiple target genes. 9 Abnormal expression levels of various lncRNAs have been reported in endometrial cancer and affect patient prognosis. 10,11 e lncRNA MIR210 (MIR210HG), an miR-210 host gene located in 21q13.3, is 567 nucleotides in length, 12 highly expressed in hepatocellular carcinoma (HCC) and colon cancer, and associated with poor prognosis. 13,14 In invasive breast and osteosarcoma cells, MIR210HG regulates cell invasion and migration through the epithelial-mesenchymal transition (EMT) pathway. 15,16 The expression and the underlying mechanism of MIR210HG in endometrial cancer remains unknown. > Metastasis is the leading cause of cancer-related deaths. Cancer cell metastasis is a multi-step process involving local infiltration and colonization. 17 EMT is the process by which epithelial cells are transformed into mesenchymal cells, which are involved in the malignant progression of tumors. 18

[12] Expression of p53 and PTEN in human primary endometrial carcinomas: Clinicopathological and immunohistochemical analysis and study of their concomitant expression

• Authors: A. Stavropoulos, M. Varras, T. Vasilakaki, V. Varra, A. Tsavari et al.
• Year: 2019
• Venue: Oncology Letters
• URL: https://www.semanticscholar.org/paper/d062d52025543ca9b229967849a25fa1ea2812d3
• DOI: 10.3892/ol.2019.10093
• PMID: 30944646
• PMCID: 6444490
• Citations: 30
• Summary: The combined expression of p53 and PTEN in the development of high-grade endometrial carcinoma in older patients is suggested, which suggested an intrinsic association between expression levels of these tumor suppressor genes.
• Evidence snippets:
• Snippet 1 (score: 0.437) > hyperplasia and have hormone-receptor positivity. However, type II endometrial carcinoma is a less common type of serous or clear cell adenocarcinoma, accounting for only ~10% of endometrial tumors. They are poorly differentiated, estrogen-independent tumors, which are associated with atrophic endometrium and have poorer outcomes (8,9). Endometrial carcinoma is believed to arise from a variety of genetic alterations involving signaling pathways, activation of proto-oncogenes and inactivation of tumor suppressor genes. > The development and progression of each group of endometrial carcinoma follows distinct molecular mechanisms of oncogenesis, reflecting the presence of type-specific genetic alterations. Although there are well-established surgical, radio-and chemotherapeutic treatments, the identification and characterization of biomarkers is necessary for improving the understanding of molecular pathways of the disease and for the development of specific novel molecular targeted therapies, with the aim to achieve greater specificity in tumor progression and metastatic processes, and to accurately evaluate the prognosis, particularly for recurrent and unfavorable disease course (3,5,10,11). Phosphatase and tensin homolog (PTEN) was identified in 1997, and is a tumor suppressor gene located on chromosome 10 (10q23) that suppresses cell proliferation and differentiation and is involved in the insulin signaling pathway. The protein encoded by this gene is a 55-kDa protein composed of 403 amino acids, which has protein tyrosine phosphatase activities. PTEN protein negatively regulates the phosphatidylinositol 3-kinase (PI3K) signaling pathway. A downstream effector that emanates from PI3K is the Akt protein, which is a serine-threonine kinase. Therefore, PTEN protein can act through the Akt signaling pathway (12)(13)(14). PTEN protein under normal physiological conditions has an antagonistic effect on intracellular signaling pathways induced by integrin or growth factors. Furthermore, PTEN protein inhibits intracellular signaling, cell proliferation, cell migration and cellular adhesion formation.

[13] Metformin inhibits 17β-estradiol-induced epithelial-to-mesenchymal transition via βKlotho-related ERK1/2 signaling and AMPKα signaling in endometrial adenocarcinoma cells

• Authors: Zhao Liu, Shasha Qi, Xingbo Zhao, Mingjiang Li, S. Ding et al.
• Year: 2016
• Venue: Oncotarget
• URL: https://www.semanticscholar.org/paper/04863739f0c0d64f053433be7e5cff87b08c3216
• DOI: 10.18632/oncotarget.7040
• PMID: 26824324
• PMCID: 5008287
• Citations: 45
• Influential citations: 2
• Summary: Metformin abolishes 17β-estradiol-induced cell proliferation and EMT in endometrial adenocarcinoma cells by upregulating βKlotho expression, inhibiting ERK1/2 signaling, and activating AMPKα signaling.
• Evidence snippets:
• Snippet 1 (score: 0.434) > Endometrial adenocarcinoma is the most common gynecological cancer worldwide [1], and one-half of patients died for advanced disease [2]. A better understanding of mechanism underlying the progress of endometrial carcinoma is required to facilitate the development of effective therapeutic strategies. > A series of reports indicate that the epithelialmesenchymal transition (EMT) plays an important role in the tumorigenesis, progression, and chemoresistance of multiple carcinomas [3][4][5], including endometrial carcinoma [6]. During the EMT, epithelial cells undergo extensive alterations in gene expression, resulting in the loss of apical-basal polarity, the severing of intercellular adhesive junctions, and the degradation of basement membrane components [7]. In this way, they become mesenchymal cells with the characteristics of increased migration and invasion. The loss of E-cadherin is generally accepted as a hallmark of the EMT [8], which reduces cell-cell adhesion and destabilizes the epithelial architecture. This process is accompanied by increased expression of mesenchymal-related proteins, including N-cadherin, Vimentin, and fibronectin, which bestow a motile phenotype on cancer cells through changes in cellular architecture and cell-matrix interactions [9,10]. Many transcription factors, such as Snail and Slug, act as repressors of E-cadherin in response to TGF-β [11] and IGF-IR [12] signaling, and have been linked to the induction of the EMT under different cellular contexts. In endometrial carcinoma, alterations of EMT-related markers have been associated with metastatic disease and reduced survival [13,14]. Although the EMT has been broadly described in endometrial carcinoma, the molecular pathways involved are still poorly delineated. > As a hormone-dependent disease, endometrial carcinomas are sensitive to endogenous and exogenous estrogens, which are known risk factors for the disease.

[14] Nasopharyngeal Carcinoma Signaling Pathway: An Update on Molecular Biomarkers

• Authors: W. Tulalamba, T. Janvilisri
• Year: 2012
• Venue: International Journal of Cell Biology
• URL: https://www.semanticscholar.org/paper/307cb9186444d9dad6e2e3b53763be0de76de186
• DOI: 10.1155/2012/594681
• PMID: 22500174
• PMCID: 3303613
• Citations: 93
• Influential citations: 5
• Summary: The molecular signaling pathways in the NPC are discussed for the holistic view of NPC development and progression and the important insights toward NPC pathogenesis may offer strategies for identification of novel biomarkers for diagnosis and prognosis.
• Evidence snippets:
• Snippet 1 (score: 0.431) > In the pregenomic eras, highly integrated and complex circuitry of molecular signaling in NPC pathogenesis was only partially understood. Over the past decade, the knowledge of the molecular mechanisms in NPC carcinogenesis has been rapidly accumulated. Dysregulation and abnormal protein expression of molecules in certain signaling pathways involved in cellular functions including proliferation, adhesion, survival, and apoptosis has been demonstrated in the NPC cells. Detailed information on the complex network in signaling pathway leading to a coordinated pattern of gene expression and regulation in NPC will undoubtedly provide important clues to develop novel prognostic and therapeutic strategies for this cancer. Refining molecular markers into clinically relevant assays may assist in the detection of NPC in asymptomatic patients, as well as stage classification and monitoring disease progression and treatments. Furthermore, selective regulation of particular proteins targeting cancer cell proliferation, invasion, and apoptosis is a hopeful prospect for future anticancer therapy that slow disease progression and improve survival.

[15] Role of Pyroptosis in Endometrial Cancer and Its Therapeutic Regulation

• Authors: Abdullah Al Mamun, Peiwu Geng, Shuanghua Wang, Chuxiao Shao
• Year: 2024
• Venue: Journal of Inflammation Research
• URL: https://www.semanticscholar.org/paper/c5b868c76c61139f227792dd7d74139330ba76fd
• DOI: 10.2147/JIR.S486878
• PMID: 39377044
• PMCID: 11457779
• Citations: 7
• Summary: The molecular mechanisms of pyroptosis-dependent signaling pathways and their contributory role and function in advancing EC are presented and new insights into potential future applications and innovative approaches in utilizing pyroptosis to develop effective anti-cancer therapies are offered.
• Evidence snippets:
• Snippet 1 (score: 0.424) > Endometrial cancer (EC) is the predominant form of gynecologic malignancy worldwide. The incidence of EC is approximately 142,000 women per year with an estimated 42,000 women dying from this disease. 1 There is currently a predominant role for surgical interventions in the management of patients without reproductive needs. 2 However, patients with elevated risk factors may require additional treatment techniques such as radiation and chemotherapy. These therapeutic approaches promote ROS-mediated stress and induce apoptosis in cancer cells. Cancer-related deficiencies in apoptosis initiation may occur, but there is also the possibility of an "oncogene addiction" phenomenon that can result in treatment ineffectiveness. 3 Cancer cells are exquisitely dependent upon a single oncogenic lesion through many genetic and epigenetic changes during the development of their neoplastic characteristics. It was found in a laboratory setting that tumor cells could depend on tumor cells when an oncogene was suppressed or tumor suppressor expression was restored, which led to the initial suggestion that the developemnt of tumor cells could depend on tumor cells. These first discoveries suggested that therapeutic drugs aimed at the repair or regulation of these mutant gene products might have broad effectiveness in the treatment of EC. Apoptosis, necroptosis and pyroptosis are discrete cellular mechanisms of programmed cell death within host cells. 4,5 7][18] In addition, pyroptosis plays a key role in the onset and advancement of several inflammatory conditions, particularly in the conversion of organ or cell inflammation into cancer. > The purpose of this study was to find, screen and evaluate information on inflammasomes and pyroptosis-dependent cell death in EC including information obtained from Elsevier, Google Scholar, PubMed, Science Direct, Scirus, Sci Finder, Scopus, Springer and Web of Science. We also identified potential therapeutic compounds that may be used to suggest and control these mechanisms. Furthermore, we used local and international books and peer-reviewed journals to find relevant information. This review also discusses the molecular mechanisms of pyroptosis-related signaling pathways and their contributory roles in the pathogenesis and progression of EC.

[16] Immune microenvironment and molecular mechanisms in endometrial cancer: implications for resistance and innovative treatments

• Authors: Yijia Chen, Lai Jiang, Lanyue Zhang, Hao Chi, Qin Wang
• Year: 2025
• Venue: Discover Oncology
• URL: https://www.semanticscholar.org/paper/e4bf86df7fdfb4a1eb54ad7e0b4bac9d1e935ca8
• DOI: 10.1007/s12672-025-02169-z
• PMID: 40237942
• PMCID: 12003227
• Citations: 8
• Summary: Recent advances in related therapeutic strategies are summarized and emerging therapeutic strategies by targeting key pathways and modulating the immune microenvironment to overcome drug resistance and improve patient prognosis are proposed.
• Evidence snippets:
• Snippet 1 (score: 0.424) > Discover Oncology (2025) 16:532 | https://doi.org/10.1007/s12672-025-02169-z as systematic lymphadenectomy is often ineffective in advanced cases, but their importance in diagnosis and staging should not be overlooked [9]. Although radiotherapy and chemotherapy improve patient survival, they are also associated with adverse effects and drug resistance [10]. In recent years, targeted therapies and immunotherapies have gradually become a research hotspot, and immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have demonstrated significant effectiveness in clinical trial [11]. For example, a clinical trial reported a 13% objective response rate (ORR) in patients with advanced endometrial cancer treated with pembrolizumab [12]. These emerging therapies present potential advancements in the prognosis of patients diagnosed with advanced endometrial cancer. This review aimed to reveal the molecular mechanisms underlying endometrial cancer and the profound impact of the immune microenvironment on disease progression and drug resistance. Recent studies have clearly indicated that various mechanisms are involved in drug resistance among endometrial cancer cells through aberrant activation of key signaling pathways, genetic mutation, and modification of the tumor microenvironment. We explored how these resistance mechanisms affect the efficacy of existing treatments, particularly targeted therapies and immunotherapies. Simultaneously, this study assessed recent advances in relevant therapeutic strategies and suggested the possibility of emerging therapeutic strategies to address the challenges posed by drug resistance. By systematically analyzing the progress of the current research, this study provides a solid theoretical foundation for clinical applications to promote the early diagnosis and individualized treatment of endometrial cancer.

[17] P53 and Murine Double Mimute 2 (MDM2) Expression Changes and Significance in Different Types of Endometrial Lesions

• Authors: Zhongyong Jiang, Wanqing A Xu, Gang Dan, Yuan Liu, J. Xiong
• Year: 2016
• Venue: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
• URL: https://www.semanticscholar.org/paper/806b7a2b87fca90c3ccc83ded49c596e1b194ef3
• DOI: 10.12659/MSM.898616
• PMID: 27924072
• PMCID: 5158131
• Citations: 8
• Summary: P53 and MDM2 mRNA and protein were elevated in endometrial polyps andendometrial adenocarcinoma and their expressions were correlated with clinical staging of endometrian adenOCarcinomas.
• Evidence snippets:
• Snippet 1 (score: 0.420) > To date, the p53 gene shows the closest relationship with human tumors. It is involved in regulating cell cycle, cell growth, apoptosis, and cell division. Tumor suppressor gene p53 is a transcription factor that can directly or indirectly control the cell cycle genes or apoptosis-related gene expression, and is involved in the apoptosis-related death receptor pathway and mitochondrial pathway [18,19]. Wild-type p53 protein plays a negative role in regulating cell growth. P53 mutation or abnormal expression is an important mechanism of inducing tumors [20]. P53 gene mutation may lead to loss of negative regulation, resulting in abnormal cell proliferation and canceration. This study analyzed p53 mRNA and protein, which are expressed in several common types of endometrial lesions. The results confirmed that p53 mRNA and protein levels in uterine adenomyosis were similar to those in controls. Its expression was significantly elevated in the endometrial polyps group and the endometrial adenocarcinoma group, especially in endometrial adenocarcinoma. Research showed that p53 gene and protein have important roles in the process of endometrial carcinoma. P53 gene activation and increased protein expression can induce abnormal cell proliferation. Its elevation can be seen in proliferative diseases, such as endometrial polyps and cancer. P53 gene mutation and abnormal protein expression often occur in the advanced stage of endometrial adenocarcinoma, and can assist diagnosing the degree of malignancy of endometrial cancer [15,21]. > The zinc finger structure in MDM2 can mediate protein interaction and the combination of DNA and RNA. It participates in regulating cell cycle and promoting cell proliferation, thus facilitating tumor growth [22,23]. However, little is known about MDM2 expression in various endometrial lesions, including uterine adenomyosis, endometrial polyps, and endometrial carcinoma. This study confirmed that MDM2 mRNA and protein expression showed no statistically significant differences between uterine adenomyosis and normal endometrium. Its level obviously increased in endometrial polyps and endometrial adenocarcinoma, particularly in the latter.

[18] Identification of key pathways and genes in endometrial cancer using bioinformatics analyses

• Authors: Yan Liu, Teng Hua, Shuqi Chi, Hongbo Wang
• Year: 2018
• Venue: Oncology Letters
• URL: https://www.semanticscholar.org/paper/cb68cdb784810144c177cfadff2173b22f0b6b2a
• DOI: 10.3892/ol.2018.9667
• PMID: 30655845
• PMCID: 6313012
• Citations: 20
• Summary: Three overlapping genes between the DEGs and the DEM targets, BIRC5, CENPF and HJURP, were associated with significantly worse overall survival of patients with EC.
• Evidence snippets:
• Snippet 1 (score: 0.419) > Endometrial carcinoma (EC) is one of the most common gynecological cancer types, with increasing global incidence in recent years (1). A total of 60,050 cases of EC and 10,470 EC-associated cases of mortality were reported in the USA in 2016 (1), which was markedly higher than the 2012 statistics of 47,130 cases and 8,010 mortalities (2). Although numerous studies have been conducted to investigate the mechanisms of endometrial tumorigenesis and development, to the best of our knowledge, the exact etiology remains unknown. Understanding the potential molecular mechanisms underlying EC initiation and progression is of great clinical significance. Previously, microarray technologies and bioinformatics have widely been used for the differential expression analysis of cancer and healthy cells to identify novel diagnostic and therapeutic biomarkers (3). > MicroRNAs (miRNAs) are small, noncoding RNAs that regulate the expression of critical genes involved in cancer progression and treatment (4). They bind to the 3'-untranslated region (3'-UTR) of target mRNAs (5), resulting in either degradation or inhibition of the expression and function of protein-coding mRNAs. miRNAs regulate several functions in cancer cells, including proliferation, apoptosis, metastasis, immune evasion and differentiation (6). In addition, several miRNAs serve critical roles in EC pathogenesis (7,8) and are associated with clinicopathological features and survival (9). However, the specific mechanisms associated with miRNA-mediated regulation in EC require further investigation. > The current study evaluated the potential molecular mechanisms and biomarkers of EC using a bioinformatics approach. Microarray expression data were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) and miRNAs (DEMs) in the EC samples compared with normal samples were identified using the GEO2R program and R software. The DEGs were subjected to functional and pathway enrichment analysis, followed by protein-protein interaction (PPI) network and survival analysis. A putative miRNA-mRNA network relevant to EC pathogenesis was then constructed.

[19] Depleting TMED3 alleviates the development of endometrial carcinoma

• Authors: Jin Zhang, Y. Qi
• Year: 2022
• Venue: Cancer Cell International
• URL: https://www.semanticscholar.org/paper/aa3390515c54b2bddaebb7e59ad78b3179a241ce
• DOI: 10.1186/s12935-022-02649-0
• Citations: 1
• Summary: This study suggested that knocking down TMED3 affected the malignant phenotype of EC cells and thus limited tumor progression, which provided insights to the development of targeted drugs for EC treatment.
• Evidence snippets:
• Snippet 1 (score: 0.419) > As one of gynecologic tumors, endometrial carcinoma (EC) has been characterized by high incidence rate, but its molecular pathogenesis has remained unclear. TMED3 is a membrane protein and has been indicated to implicate several tumor-related diseases. In the current study, we aimed to explore the physiological function of TMED3 in EC progression. Through bioinformatic analysis using The Cancer Genome Atlas database and immunohistochemistry assay on tissue microarray, we examined whether TMED3 was upregulated in EC tissues. After constructing TMED3-knockdown cell models via lentiviral transfection, qPCR and western blot were employed to determine the expression levels of TMED3 mRNA and protein. Then, Celigo cell counting assay, CCK8 assay, flow cytometry, wound-healing assay and Transwell assay were used to detect cell proliferation, cell cycle, cell apoptosis and cell migration, respectively. As a result, it was found that TMED3 was upregulated in EC cells, which was also verified in clinical samples. We then found that downregulation of TMED3 considerably restrained cell cycle, cell growth and migration but promoted apoptosis of EC cells. The following in-vivo experiments also verified that tumor growth was inhibited after TMED3 knockdown. The exploration in molecular mechanisms showed that TMED3 deletion may weaken cellular viability through upregulating pro-apoptotic proteins and targeting PI3K/AKT signaling pathways. This study suggested that knocking down TMED3 affected the malignant phenotype of EC cells and thus limited tumor progression, which provided insights to the development of targeted drugs for EC treatment.

[20] Depleting TMED3 alleviates the development of endometrial carcinoma

• Authors: Jin Zhang, Y. Qi
• Year: 2022
• Venue: Cancer Cell International
• URL: https://www.semanticscholar.org/paper/37e8e4049ad0e56cda4a70f61827836ae8b12fe0
• DOI: 10.1186/s12935-022-02649-0
• PMID: 35854294
• PMCID: 9295347
• Citations: 2
• Summary: This study suggested that knocking down TMED3 affected the malignant phenotype of EC cells and thus limited tumor progression, which provided insights to the development of targeted drugs for EC treatment.
• Evidence snippets:
• Snippet 1 (score: 0.417) > Background As one of gynecologic tumors, endometrial carcinoma (EC) has been characterized by high incidence rate, but its molecular pathogenesis has remained unclear. TMED3 is a membrane protein and has been indicated to implicate several tumor-related diseases. In the current study, we aimed to explore the physiological function of TMED3 in EC progression. Methods Through bioinformatic analysis using The Cancer Genome Atlas database and immunohistochemistry assay on tissue microarray, we examined whether TMED3 was upregulated in EC tissues. After constructing TMED3-knockdown cell models via lentiviral transfection, qPCR and western blot were employed to determine the expression levels of TMED3 mRNA and protein. Then, Celigo cell counting assay, CCK8 assay, flow cytometry, wound-healing assay and Transwell assay were used to detect cell proliferation, cell cycle, cell apoptosis and cell migration, respectively. Results As a result, it was found that TMED3 was upregulated in EC cells, which was also verified in clinical samples. We then found that downregulation of TMED3 considerably restrained cell cycle, cell growth and migration but promoted apoptosis of EC cells. The following in-vivo experiments also verified that tumor growth was inhibited after TMED3 knockdown. The exploration in molecular mechanisms showed that TMED3 deletion may weaken cellular viability through upregulating pro-apoptotic proteins and targeting PI3K/AKT signaling pathways. Conclusions This study suggested that knocking down TMED3 affected the malignant phenotype of EC cells and thus limited tumor progression, which provided insights to the development of targeted drugs for EC treatment.

Notes

• This provider combines search_papers_by_relevance with snippet_search.
• No synthesis or second-stage model call is performed.

1. Disease Information

1.1 Overview (current understanding)

Endometrial carcinoma (EC) is a heterogeneous malignancy arising from the endometrial lining of the uterine corpus. Contemporary clinical management is increasingly guided by integrated histologic and molecular classification, particularly the four-group TCGA/ProMisE framework (POLE-mutated, mismatch repair deficient, p53-abnormal, and no specific molecular profile), which stratifies prognosis and influences treatment selection. (kuhn2024unsolvedissuesin pages 1-2, kuhn2024unsolvedissuesin pages 5-6, ribeirosantos2024tailoringendometrialcancer pages 2-3)

1.2 Synonyms and alternative names

Commonly used synonyms in the literature include endometrial cancer, endometrial carcinoma, and uterine corpus cancer (often grouped under “uterine cancer” in registry statistics and clinical practice discussions). (rodriguez2025trendsinendometrial pages 1-2, guo2025trendsinendometrial pages 15-18)

1.3 Key identifiers (ICD/MeSH/MONDO)

The retrieved full-text sources used here did not explicitly provide ICD-10/ICD-11 codes, MeSH IDs, or MONDO IDs for endometrial carcinoma. Where ontology identifiers are required for knowledge-base population, an additional targeted ontology lookup (e.g., MONDO/MeSH/ICD browsers) is needed beyond the currently retrieved corpus. (kuhn2024unsolvedissuesin pages 4-5, kuhn2024unsolvedissuesin pages 1-2)

1.4 Evidence provenance (patient vs aggregated)

Most information summarized here derives from aggregated evidence: randomized phase III trials, national cancer registries (SEER/USCS-based analyses), and systematic reviews/meta-analyses. (tubridy2024treatmentofnodepositive pages 7-8, eskander2023pembrolizumabpluschemotherapy pages 6-7, guo2025trendsinendometrial pages 4-12, clarke2018associationofendometrial pages 1-2)

2. Etiology

2.1 Causal factors and major mechanistic contributors

A major etiologic axis for many endometrioid endometrial carcinomas is estrogen-driven proliferative signaling (classically described in the Bokhman “Type I” pathway), whereas more aggressive non-endometrioid subtypes align with “Type II” biology in the historical dualistic model. (ribeirosantos2024tailoringendometrialcancer pages 2-3)

2.2 Risk factors

2.2.1 Genetic risk factors

• Lynch syndrome / mismatch repair (MMR) genes: A subset of EC is associated with germline pathogenic variants affecting DNA mismatch repair (MLH1, MSH2, MSH6, PMS2). In a recent molecular-classification review, Lynch syndrome is estimated to account for ~2–5% of endometrial cancers, while MMR/MSI alterations are much more common at the tumor level. (ribeirosantos2024tailoringendometrialcancer pages 2-3)

2.2.2 Environmental and lifestyle risk factors

• Obesity: A large U.S. incidence trends analysis (2001–2021) highlights obesity as a dominant contributor, stating that ~60% of U.S. endometrial cancers are linked to obesity. (guo2025trendsinendometrial pages 15-18)

2.3 Protective factors

Protective factors were not quantified in the retrieved endometrial-cancer-specific sources in this run; additional targeted searches (e.g., for hormonal contraception, parity, metformin/aspirin, weight loss interventions) would be required for evidence-backed estimates.

2.4 Gene–environment interactions

The retrieved sources did not provide direct quantitative gene–environment interaction estimates for EC. Mechanistically, interactions are plausible (e.g., obesity/hyperestrogenism interacting with PI3K pathway lesions), but specific GxE statistics were not extractable from the accessed documents.

3. Phenotypes (clinical presentation)

3.1 Key presenting features and frequencies

Postmenopausal bleeding (PMB) is a dominant presenting symptom: - Meta-analysis: pooled prevalence of PMB among women with endometrial cancer = 91% (95% CI 87–93%). (clarke2018associationofendometrial pages 1-2) - Meta-analysis: pooled risk of endometrial cancer among women presenting with PMB = 9% (95% CI 8–11%). (clarke2018associationofendometrial pages 1-2) - Danish nationwide cohort (43,756 PMB patients): absolute risk of endometrial cancer after a first-time hospital PMB diagnosis was 4.66% at 1 year and 5.18% at 5 years. (bengtsen2019firsttimepostmenopausalbleeding pages 5-6)

3.2 Onset and course

Typical onset is adult/postmenopausal; however, incidence is rising among younger (premenopausal) women in U.S. registry analyses. (guo2025trendsinendometrial pages 4-12)

3.3 Quality of life impact

The retrieved sources did not provide disease-specific quantitative QoL instruments (e.g., EQ-5D, SF-36) or PROMIS metrics for EC in this run; however, symptom-driven care seeking (e.g., response to PMB) has recognized patient-level implications for timely diagnosis. (clarke2018associationofendometrial pages 1-2)

3.4 Suggested HPO terms (non-exhaustive)

• Postmenopausal vaginal bleeding (HPO suggestion; commonly mapped as abnormal uterine bleeding in ontologies)
• Abnormal uterine bleeding
• Pelvic pain (noted as common in diagnostic triage datasets) (doll2024endometrialthicknessas pages 1-2)

(Exact HPO IDs were not provided in the accessed texts and should be mapped via HPO lookup.)

4. Genetic/Molecular Information

4.1 Core molecular taxonomy (TCGA/ProMisE)

Endometrial carcinoma is commonly categorized into four major molecular groups used in routine practice: POLE-mutated, MMR-deficient (MSI-hypermutated), p53-abnormal (copy-number high/serous-like), and NSMP (no specific molecular profile; copy-number low). (kuhn2024unsolvedissuesin pages 1-2, kuhn2024unsolvedissuesin pages 5-6, ribeirosantos2024tailoringendometrialcancer pages 2-3)

Table: This table summarizes the four TCGA/ProMisE molecular subtypes of endometrial carcinoma, the routine biomarkers/tests used to classify them, their usual prognostic implications, and representative frequent alterations reported in the provided evidence snippets.

4.2 Frequently altered genes and pathways (somatic)

Across subtypes, commonly discussed alterations include: - PI3K pathway lesions and genes including PTEN, PIK3CA, and others; NSMP/copy-number low is described as often having PI3K pathway alterations. (ribeirosantos2024tailoringendometrialcancer pages 2-3) - TP53 mutations are frequent in the copy-number high/p53-abnormal group and are reported as common in non-endometrioid carcinomas; serous-like tumors may also show HER2 amplification. (ribeirosantos2024tailoringendometrialcancer pages 2-3) - MMR gene loss (MLH1, MSH2, MSH6, PMS2) characterizes the MSI/MMRd group. (ribeirosantos2024tailoringendometrialcancer pages 2-3)

4.3 Epigenetics

MMR deficiency in EC can be driven by mechanisms including MLH1-related events; however, detailed epigenetic mechanisms (e.g., methylation subtype frequencies, chromatin programs) were not comprehensively extractable from the retrieved endometrial-cancer-specific texts in this run. (ribeirosantos2024tailoringendometrialcancer pages 2-3)

5. Environmental Information

This run retrieved limited EC-specific information beyond obesity-related burden. Environmental toxicant exposures and infectious etiologies were not supported by the accessed full texts; additional CTD/epidemiology searches would be required.

6. Mechanism / Pathophysiology

6.1 Conceptual causal chains (molecular-to-clinical)

• MMRd/MSI pathway: Loss of MMR protein function (tumor or germline) → increased mutation burden (MSI/hypermutation) → increased neoantigenicity → enhanced responsiveness to immune checkpoint blockade; clinically, this is reflected by substantially larger chemoimmunotherapy benefit in dMMR tumors versus pMMR in phase III trials. (ribeirosantos2024tailoringendometrialcancer pages 2-3, tubridy2024treatmentofnodepositive pages 7-8, eskander2023pembrolizumabpluschemotherapy pages 6-7)
• p53-abnormal/copy-number high pathway: TP53 dysfunction and copy-number alterations → aggressive biology and poorer outcomes, motivating intensified systemic strategies and molecularly informed staging. (kuhn2024unsolvedissuesin pages 1-2, ribeirosantos2024tailoringendometrialcancer pages 2-3, berek2023figostagingof pages 12-14)

6.2 Pathways and processes (suggested ontology mappings)

Evidence-supported pathway suggestions (to be mapped to GO/Reactome/KEGG IDs): - DNA mismatch repair (MMRd group) (ribeirosantos2024tailoringendometrialcancer pages 2-3) - PI3K/AKT signaling (common alterations in NSMP/copy-number low) (ribeirosantos2024tailoringendometrialcancer pages 2-3) - p53-mediated DNA damage response / cell-cycle control (p53abn group) (ribeirosantos2024tailoringendometrialcancer pages 2-3)

Suggested GO biological process terms (text-supported but not explicitly enumerated in sources): DNA repair; regulation of cell cycle; apoptotic signaling.

Suggested CL (cell types) and UBERON (anatomy) are in Section 7.

7. Anatomical Structures Affected

7.1 Organ and tissue level

• Primary: uterine corpus endometrium (endometrium of the uterus).
• Spread: clinically relevant metastatic patterns include pelvic/para-aortic lymph nodes and distant sites; orthotopic xenograft models recapitulate metastatic spread to clinically relevant locations. (yildiz2024murinexenograftmodels pages 10-12)

7.2 Cell types (CL suggestions)

• Endometrial glandular epithelial cells (carcinoma origin)
• Tumor-associated stromal fibroblasts (noting stromal replacement by murine stroma in xenografts) (yildiz2024murinexenograftmodels pages 5-6)
• Tumor-infiltrating lymphocytes (e.g., CD8+ T cells) in immunotherapy-responsive contexts (supported indirectly through immunotherapy responsiveness; detailed cell ontology mapping not provided in retrieved EC-specific texts).

7.3 Subcellular compartments (GO CC suggestions)

• Nucleus (DNA repair defects)
• Cytosol/cell membrane (signaling pathway dysregulation)

(Explicit GO cellular component IDs were not provided in the accessed texts.)

8. Temporal Development

8.1 Onset

• Rising incidence is documented both in premenopausal and postmenopausal groups in U.S. registry analyses, with particularly notable increases in ages 20–49 and ≥70 years. (guo2025trendsinendometrial pages 4-12)

8.2 Progression and staging

• Clinical course spans early-stage (often uterine-confined) through regional/distant spread.
• Modern staging has evolved to incorporate molecular markers for prognostic precision (FIGO 2023). (berek2023figostagingof pages 12-14)

9. Inheritance and Population

9.1 Epidemiology and disparities (recent registry analyses)

• U.S. incidence is increasing, with disproportionate increases among women of color in SEER-based analyses. In one analysis (2000–2019), early-onset (<50) average annual percent changes were highest in American Indian/Alaska Native women (4.8), followed by Black (3.3), Hispanic/Latina (3.1), and Asian/Pacific Islander women (2.4), with White women lowest (0.9). (rodriguez2025trendsinendometrial pages 1-2)
• Another U.S. registry analysis (2001–2021; hysterectomy-adjusted) reports incidence increases among ages 20–49 (86.8 to 113.8 per 1,000,000) and notes case-count declines in 2020 with an increased proportion of distant-stage cases consistent with pandemic-related diagnostic disruption. (guo2025trendsinendometrial pages 4-12)

9.2 Hereditary fraction

Lynch syndrome accounts for a minority of EC cases (estimated ~2–5% in a molecular pathology review), but tumor-level MMR deficiency is substantially more common and clinically actionable. (ribeirosantos2024tailoringendometrialcancer pages 2-3)

10. Diagnostics

10.1 Symptom-triggered evaluation

Given the high prevalence of PMB among EC cases (91%), PMB is a key clinical trigger for diagnostic workup. (clarke2018associationofendometrial pages 1-2)

10.2 Imaging and endometrial thickness (ET) triage

Transvaginal ultrasound (TVUS) ET thresholds are widely used but have limitations: - A cohort study of women with bleeding found that ET alone did not always provide meaningful stratification for initial PMB presentations; in 593 PMB patients, EC prevalence was 7.9% and EIN 3.0%. (clarke2020riskassessmentof pages 1-2) - In Black individuals, a JAMA Oncology diagnostic study found that with a <5 mm ET triage threshold, 11.4% of EC cases would be missed; even at 4 mm the false-negative probability was 9.5%. The authors concluded ET triage is not reliable in this population and stated that with postmenopausal bleeding, tissue sampling (biopsy) is strongly recommended. (doll2024endometrialthicknessas pages 1-2) - Review evidence notes that persistent or recurrent bleeding warrants endometrial examination regardless of ET; it also notes a meaningful fraction (25–34%) of type II cancers may present with thin/unclear endometrial echo, limiting TVUS utility. (asaturova2024advancementsinminimally pages 2-4)

10.3 Tissue diagnosis and pathology

• Endometrial biopsy (e.g., pipelle) and/or hysteroscopy with histopathology remain central to diagnosis; recurrent PMB pathways often escalate to hysteroscopy. (ghoubara2018endometrialpathologyin pages 8-12)

10.4 Molecular pathology implementation

WHO-endorsed stepwise classification uses POLE sequencing → MMR IHC → p53 IHC to assign tumors to POLEmut, MMRd, p53abn, or NSMP. (kuhn2024unsolvedissuesin pages 5-6)

10.5 FIGO 2023 staging (molecular integration)

FIGO 2023 integrates molecular classification into staging and recommends complete molecular classification. (berek2023figostagingof pages 12-14) - In early stages, POLEmut and p53abn can modify stage (e.g., IAmPOLEmut; IICmp53abn), while MMRd and NSMP do not by themselves change stage. (berek2023figostagingof pages 12-14) - Empirical cohort (China, 547 patients): 26.9% experienced stage shifts under FIGO 2023; 63 FIGO 2009 stage I–II cases were reclassified as IAmPOLEmut and 53 as IICmp53abn. (yu2024clinicalapplicationof pages 1-2)

10.6 Differential diagnosis

Not systematically extractable from the accessed sources in this run; typical differentials include benign causes of abnormal bleeding (atrophy, polyps) and endometrial intraepithelial neoplasia.

11. Outcome / Prognosis

11.1 Prognostic stratification by molecular class

Molecular subgroup is prognostic: POLEmut is associated with excellent outcomes, p53abn with the worst outcomes, and MMRd/NSMP with intermediate outcomes. (kuhn2024unsolvedissuesin pages 1-2, kuhn2024unsolvedissuesin pages 5-6)

11.2 Prognosis in key systemic-therapy settings

In advanced/recurrent settings, randomized trials show substantial improvements in progression-free survival for chemoimmunotherapy, especially in dMMR tumors (see Treatment section). (tubridy2024treatmentofnodepositive pages 7-8, eskander2023pembrolizumabpluschemotherapy pages 6-7)

12. Treatment

12.1 Key concepts (current standard and rapidly evolving areas)

Systemic therapy is increasingly molecularly and biomarker guided, especially by MMR status and integrated TCGA/ProMisE class. The “front-line” (first-line) paradigm for advanced/recurrent disease has shifted toward adding PD-1/PD-L1 blockade to platinum-taxane chemotherapy based on 2023 NEJM phase III trials. (tubridy2024treatmentofnodepositive pages 7-8, eskander2023pembrolizumabpluschemotherapy pages 6-7)

12.2 Surgery and radiation (standard of care backbone)

The retrieved sources primarily focused on systemic therapy; they nevertheless describe node-positive management as multimodal with systemic therapy with/without radiation and evolving integration of immunotherapy and IMRT approaches. (tubridy2024treatmentofnodepositive pages 7-8)

12.3 Systemic therapy: pivotal trials (2023–2024 prioritized)

12.3.1 Frontline chemoimmunotherapy

RUBY (dostarlimab + carboplatin/paclitaxel) (NEJM, Jun 2023; DOI URL in paper record) - dMMR/MSI-H subgroup: 24-month PFS 61.4% with dostarlimab vs 15.7% placebo; HR 0.28 (95% CI 0.16–0.50). (tubridy2024treatmentofnodepositive pages 7-8) - Overall population: 24-month PFS 36.1% vs 18.1%; HR 0.64; and 24-month OS 71.3% vs 56.0% (as reported in accessible summaries). (ribeirosantos2024tailoringendometrialcancer pages 1-2) - Regulatory implementation: FDA approval of dostarlimab with carboplatin/paclitaxel followed by single-agent dostarlimab for primary/recurrent MMRd EC is reported as July 31, 2023. (tubridy2024treatmentofnodepositive pages 8-9)

NRG-GY018 (pembrolizumab + carboplatin/paclitaxel) (NEJM, Jun 2023; DOI URL in paper record) - dMMR cohort: 12-month freedom from progression/death 74% vs 38%; HR 0.30 (95% CI 0.19–0.48; P<0.001). (eskander2023pembrolizumabpluschemotherapy pages 6-7) - pMMR cohort: median PFS 13.1 months vs 8.7 months; HR 0.54 (95% CI 0.41–0.71; P<0.001). (eskander2023pembrolizumabpluschemotherapy pages 6-7)

12.3.2 Immunotherapy + PARP inhibition strategy

DUO-E (durvalumab + carboplatin/paclitaxel → maintenance durvalumab ± olaparib) (JCO, Jan 2024; DOI URL in paper record) - Review-reported primary results: ITT PFS HR 0.71 for durvalumab vs control and 0.55 for durvalumab+olaparib vs control; subgroup PFS benefit was observed in both dMMR and pMMR cohorts. (shim2024majorclinicalresearch pages 3-5)

12.3.3 Second-line / previously treated advanced disease (pMMR emphasis)

Study 309 / KEYNOTE-775 update (lenvatinib + pembrolizumab vs chemotherapy) (JCO, Jun 2023) - Updated efficacy: OS benefit in pMMR (HR 0.70) and all-comers (HR 0.65); PFS benefit in pMMR (HR 0.60) and all-comers (HR 0.56); ORR improved (pMMR 32.4% vs 15.1%; all-comers 33.8% vs 14.7%). (luvero2024oldissuesand pages 5-6)

12.4 Real-world implementation examples

• A multicenter retrospective study (Russia; pMMR/MSS recurrent/metastatic EC) reported median PFS 7.75 months and partial response 24% with lenvatinib+pembrolizumab; dose reductions occurred in 44%. (luvero2024oldissuesand pages 5-6)

12.5 Treatment ontology suggestions (MAXO; examples)

(Exact MAXO IDs not provided in accessed texts; suggested mappings) - Hysterectomy / surgical resection - External beam radiation therapy - Brachytherapy - Platinum-based chemotherapy (carboplatin) - Taxane chemotherapy (paclitaxel) - PD-1 inhibitor therapy (pembrolizumab, dostarlimab) - PD-L1 inhibitor therapy (durvalumab) - Multimodal chemoimmunotherapy - Tyrosine kinase inhibitor therapy (lenvatinib) - PARP inhibitor therapy (olaparib)

13. Prevention

13.1 Primary prevention

Obesity reduction is a major prevention lever given the strong contribution of obesity to EC burden in U.S. analyses. (guo2025trendsinendometrial pages 15-18)

13.2 Secondary prevention / early detection

No population-wide screening program is established in the retrieved sources; rather, symptom-triggered evaluation (particularly PMB) is central. PMB-focused strategies can potentially identify ~90% of EC cases because PMB prevalence among EC is ~91%, although most PMB presentations are not cancer. (clarke2018associationofendometrial pages 1-2)

13.3 High-risk hereditary prevention

The accessed corpus confirms Lynch syndrome relevance and emphasizes molecular tumor testing (MMR IHC/MSI) as a practical gateway to identify patients who may need genetic counseling/testing; however, detailed prophylaxis timing and guideline algorithms were not fully extractable here. (ribeirosantos2024tailoringendometrialcancer pages 2-3)

14. Other Species / Natural Disease

No comparative veterinary natural-disease evidence was retrieved in the accessed documents for this run.

15. Model Organisms / Preclinical Models

15.1 Xenograft and PDX models

• Uterine corpus malignancy PDX establishment: 52 PDX models from 92 patient tumors (56.5% success) with similarity of pathology and gene profiles between primary and PDX tumors. (ueda2024consistencybetweenprimary pages 1-2)
• A xenograft-model review reports broad engraftment variability by histology and implantation method; limitations include murine stromal replacement, selection biases, and long timelines. (yildiz2024murinexenograftmodels pages 5-6)

15.2 Organoid-based models and organoid-derived xenografts

• Organoid-based patient-derived xenograft (O-PDX) mouse model (Frontiers in Oncology, May 2024) demonstrated that an MRI radiomics signature could predict response over time; reported AUCs increased from 0.38 (baseline) to 1.0 (endpoint) in the orthotopic cohort, with external validation AUC 0.85 at day 10/endpoint. (espedal2024mriradiomicscaptures pages 1-2)

15.3 Limitations noted by experts

Preclinical model limitations include long establishment times, incomplete immune microenvironment representation (especially in xenografts), and potential divergence over passages; therefore, continued development of immunocompetent or humanized models is highlighted as a major need. (yildiz2024murinexenograftmodels pages 5-6, yildiz2024murinexenograftmodels pages 17-19)

Expert synthesis (2023–2024 emphasis)

A convergent theme across 2023–2024 literature is that EC is no longer best conceptualized as a single disease entity; instead, integrated histo-molecular classification and FIGO 2023 staging are driving risk stratification and therapeutic personalization. The magnitude of benefit seen in dMMR tumors in frontline chemoimmunotherapy (e.g., NRG-GY018 and RUBY) provides clinical proof that mechanistic tumor features (MMR status) are predictive and actionable. (eskander2023pembrolizumabpluschemotherapy pages 6-7, tubridy2024treatmentofnodepositive pages 7-8, berek2023figostagingof pages 12-14)

URLs and publication dates (examples of core sources used)

• Eskander RN et al. “Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer.” NEJM (Jun 2023). https://doi.org/10.1056/NEJMoa2302312 (eskander2023pembrolizumabpluschemotherapy pages 6-7)
• Mirza MR et al. “Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer.” NEJM (Jun 2023). https://doi.org/10.1056/NEJMoa2216334 (ribeirosantos2024tailoringendometrialcancer pages 1-2)
• Westin SN et al. DUO-E trial report. JCO (Jan 2024). https://doi.org/10.1200/JCO.23.02132 (westin2024durvalumabpluscarboplatinpaclitaxel pages 2-4)
• Makker V et al. KEYNOTE-775 update. JCO (Jun 2023). https://doi.org/10.1200/JCO.22.02152 (luvero2024oldissuesand pages 5-6)
• Berek JS et al. “FIGO staging of endometrial cancer: 2023.” Int J Gynecol Obstet (Jun 2023). https://doi.org/10.1002/ijgo.14923 (berek2023figostagingof pages 12-14)
• Doll KM et al. Endometrial thickness triage in Black individuals. JAMA Oncology (Aug 2024). https://doi.org/10.1001/jamaoncol.2024.1891 (doll2024endometrialthicknessas pages 1-2)
• Clarke MA et al. PMB meta-analysis. Obstet Gynecol Surv (Dec 2018). https://doi.org/10.1097/OGX.0000000000000623 (clarke2018associationofendometrial pages 1-2)

Notable evidence gaps in this run (for knowledge-base completion)

• Formal ICD/MeSH/MONDO identifiers were not found in the accessed full texts.
• Comprehensive, evidence-backed protective factors, environmental toxicants, differential diagnosis lists, and QoL instrument statistics were not retrievable from the current document set and require targeted retrieval.

References

1. (kuhn2024unsolvedissuesin pages 1-2): Elisabetta Kuhn, Donatella Gambini, Letterio Runza, Stefano Ferrero, Giovanna Scarfone, Gaetano Bulfamante, and Ayse Ayhan. Unsolved issues in the integrated histo-molecular classification of endometrial carcinoma and therapeutic implications. Cancers, 16:2458, Jul 2024. URL: https://doi.org/10.3390/cancers16132458, doi:10.3390/cancers16132458. This article has 7 citations.

2. (kuhn2024unsolvedissuesin pages 5-6): Elisabetta Kuhn, Donatella Gambini, Letterio Runza, Stefano Ferrero, Giovanna Scarfone, Gaetano Bulfamante, and Ayse Ayhan. Unsolved issues in the integrated histo-molecular classification of endometrial carcinoma and therapeutic implications. Cancers, 16:2458, Jul 2024. URL: https://doi.org/10.3390/cancers16132458, doi:10.3390/cancers16132458. This article has 7 citations.

3. (ribeirosantos2024tailoringendometrialcancer pages 2-3): Pedro Ribeiro-Santos, Carolina Martins Vieira, Gilson Gabriel Viana Veloso, Giovanna Vieira Giannecchini, Martina Parenza Arenhardt, Larissa Müller Gomes, Pedro Zanuncio, Flávio Silva Brandão, and Angélica Nogueira-Rodrigues. Tailoring endometrial cancer treatment based on molecular pathology: current status and possible impacts on systemic and local treatment. International Journal of Molecular Sciences, 25:7742, Jul 2024. URL: https://doi.org/10.3390/ijms25147742, doi:10.3390/ijms25147742. This article has 21 citations.

4. (rodriguez2025trendsinendometrial pages 1-2): Victoria E Rodriguez, Sora Park Tanjasiri, Annie Ro, Michael A Hoyt, Robert E Bristow, and Alana M W LeBrón. Trends in endometrial cancer incidence in the united states by race/ethnicity and age of onset from 2000 to 2019. American journal of epidemiology, 194:103-113, Jul 2025. URL: https://doi.org/10.1093/aje/kwae178, doi:10.1093/aje/kwae178. This article has 19 citations and is from a domain leading peer-reviewed journal.

5. (guo2025trendsinendometrial pages 15-18): Fangjian Guo, Victor Adekanmbi, Christine D. Hsu, Thao N. Hoang, Pamela T. Soliman, Jacques G. Baillargeon, and Abbey B. Berenson. Trends in endometrial cancer incidence among premenopausal and postmenopausal women in the united states between 2001 and 2021. Cancers, 17:1035, Mar 2025. URL: https://doi.org/10.3390/cancers17061035, doi:10.3390/cancers17061035. This article has 11 citations.

6. (kuhn2024unsolvedissuesin pages 4-5): Elisabetta Kuhn, Donatella Gambini, Letterio Runza, Stefano Ferrero, Giovanna Scarfone, Gaetano Bulfamante, and Ayse Ayhan. Unsolved issues in the integrated histo-molecular classification of endometrial carcinoma and therapeutic implications. Cancers, 16:2458, Jul 2024. URL: https://doi.org/10.3390/cancers16132458, doi:10.3390/cancers16132458. This article has 7 citations.

7. (tubridy2024treatmentofnodepositive pages 7-8): Elizabeth A. Tubridy, Neil K. Taunk, and Emily M. Ko. Treatment of node-positive endometrial cancer: chemotherapy, radiation, immunotherapy, and targeted therapy. Current Treatment Options in Oncology, 25:330-345, Jan 2024. URL: https://doi.org/10.1007/s11864-023-01169-x, doi:10.1007/s11864-023-01169-x. This article has 21 citations and is from a peer-reviewed journal.

8. (eskander2023pembrolizumabpluschemotherapy pages 6-7): Ramez N. Eskander, Michael W. Sill, Lindsey Beffa, Richard G. Moore, Joanie M. Hope, Fernanda B. Musa, Robert Mannel, Mark S. Shahin, Guilherme H. Cantuaria, Eugenia Girda, Cara Mathews, Juraj Kavecansky, Charles A. Leath, Lilian T. Gien, Emily M. Hinchcliff, Shashikant B. Lele, Lisa M. Landrum, Floor Backes, Roisin E. O’Cearbhaill, Tareq Al Baghdadi, Emily K. Hill, Premal H. Thaker, Veena S. John, Stephen Welch, Amanda N. Fader, Matthew A. Powell, and Carol Aghajanian. Pembrolizumab plus chemotherapy in advanced endometrial cancer. New England Journal of Medicine, 388:2159-2170, Jun 2023. URL: https://doi.org/10.1056/nejmoa2302312, doi:10.1056/nejmoa2302312. This article has 768 citations and is from a highest quality peer-reviewed journal.

9. (guo2025trendsinendometrial pages 4-12): Fangjian Guo, Victor Adekanmbi, Christine D. Hsu, Thao N. Hoang, Pamela T. Soliman, Jacques G. Baillargeon, and Abbey B. Berenson. Trends in endometrial cancer incidence among premenopausal and postmenopausal women in the united states between 2001 and 2021. Cancers, 17:1035, Mar 2025. URL: https://doi.org/10.3390/cancers17061035, doi:10.3390/cancers17061035. This article has 11 citations.

10. (clarke2018associationofendometrial pages 1-2): Megan A. Clarke, Beverly J. Long, Arena Del Mar Morillo, Marc Arbyn, Jamie N. Bakkum-Gamez, and Nicolas Wentzensen. Association of endometrial cancer risk with postmenopausal bleeding in women: a systematic review and meta-analysis. Obstetrical & Gynecological Survey, 73:687-688, Dec 2018. URL: https://doi.org/10.1097/ogx.0000000000000623, doi:10.1097/ogx.0000000000000623. This article has 553 citations and is from a peer-reviewed journal.

11. (bengtsen2019firsttimepostmenopausalbleeding pages 5-6): Maria B. Bengtsen, Katalin Veres, and Mette Nørgaard. First-time postmenopausal bleeding as a clinical marker of long-term cancer risk: a danish nationwide cohort study. British Journal of Cancer, 122:445-451, Dec 2019. URL: https://doi.org/10.1038/s41416-019-0668-2, doi:10.1038/s41416-019-0668-2. This article has 29 citations and is from a domain leading peer-reviewed journal.

12. (doll2024endometrialthicknessas pages 1-2): Kemi M. Doll, Mindy Pike, Julianna Alson, Patrice Williams, Erin Carey, Til Stürmer, Mollie Wood, Erica E. Marsh, Ronit Katz, and Whitney R. Robinson. Endometrial thickness as diagnostic triage for endometrial cancer among black individuals. JAMA Oncology, 10:1068, Aug 2024. URL: https://doi.org/10.1001/jamaoncol.2024.1891, doi:10.1001/jamaoncol.2024.1891. This article has 25 citations and is from a highest quality peer-reviewed journal.

13. (kuhn2024unsolvedissuesin pages 8-9): Elisabetta Kuhn, Donatella Gambini, Letterio Runza, Stefano Ferrero, Giovanna Scarfone, Gaetano Bulfamante, and Ayse Ayhan. Unsolved issues in the integrated histo-molecular classification of endometrial carcinoma and therapeutic implications. Cancers, 16:2458, Jul 2024. URL: https://doi.org/10.3390/cancers16132458, doi:10.3390/cancers16132458. This article has 7 citations.

14. (berek2023figostagingof pages 12-14): Jonathan S. Berek, Xavier Matias‐Guiu, Carien Creutzberg, Christina Fotopoulou, David Gaffney, Sean Kehoe, Kristina Lindemann, David Mutch, and Nicole Concin. Figo staging of endometrial cancer: 2023. International Journal of Gynecology & Obstetrics, 162:383-394, Jun 2023. URL: https://doi.org/10.1002/ijgo.14923, doi:10.1002/ijgo.14923. This article has 1270 citations and is from a peer-reviewed journal.

15. (yildiz2024murinexenograftmodels pages 10-12): Merve Yildiz, Andrea Romano, and Sofia Xanthoulea. Murine xenograft models as preclinical tools in endometrial cancer research. Cancers, 16:3994, Nov 2024. URL: https://doi.org/10.3390/cancers16233994, doi:10.3390/cancers16233994. This article has 1 citations.

16. (yildiz2024murinexenograftmodels pages 5-6): Merve Yildiz, Andrea Romano, and Sofia Xanthoulea. Murine xenograft models as preclinical tools in endometrial cancer research. Cancers, 16:3994, Nov 2024. URL: https://doi.org/10.3390/cancers16233994, doi:10.3390/cancers16233994. This article has 1 citations.

17. (clarke2020riskassessmentof pages 1-2): Megan A. Clarke, Beverly J. Long, Mark E. Sherman, Maureen A. Lemens, Karl C. Podratz, Matthew R. Hopkins, Lisa J. Ahlberg, Lois J. Mc Guire, Shannon K. Laughlin-Tommaso, Jamie N. Bakkum-Gamez, and Nicolas Wentzensen. Risk assessment of endometrial cancer and endometrial intraepithelial neoplasia in women with abnormal bleeding and implications for clinical management algorithms. American Journal of Obstetrics and Gynecology, 223:549.e1-549.e13, Oct 2020. URL: https://doi.org/10.1016/j.ajog.2020.03.032, doi:10.1016/j.ajog.2020.03.032. This article has 106 citations and is from a highest quality peer-reviewed journal.

18. (asaturova2024advancementsinminimally pages 2-4): Aleksandra Asaturova, Andrew Zaretsky, Aleksandra Rogozhina, Anna Tregubova, and Alina Badlaeva. Advancements in minimally invasive techniques and biomarkers for the early detection of endometrial cancer: a comprehensive review of novel diagnostic approaches and clinical implications. Journal of Clinical Medicine, 13:7538, Dec 2024. URL: https://doi.org/10.3390/jcm13247538, doi:10.3390/jcm13247538. This article has 10 citations.

19. (ghoubara2018endometrialpathologyin pages 8-12): A. Ghoubara, S. Sundar, and A. A. A. Ewies. Endometrial pathology in recurrent postmenopausal bleeding: observational study of 385 women. Climacteric, 21:391-396, May 2018. URL: https://doi.org/10.1080/13697137.2018.1461825, doi:10.1080/13697137.2018.1461825. This article has 24 citations and is from a peer-reviewed journal.

20. (yu2024clinicalapplicationof pages 1-2): Changmin Yu, Xinhui Yuan, Qianlan Yao, Yuyin Xu, Xiaoyan Zhou, Xin Hu, Huijuan Yang, Huaying Wang, Xiaoli Zhu, and Yulan Ren. Clinical application of figo 2023 staging system of endometrial cancer in a chinese cohort. BMC Cancer, Jul 2024. URL: https://doi.org/10.1186/s12885-024-12633-8, doi:10.1186/s12885-024-12633-8. This article has 12 citations and is from a peer-reviewed journal.

21. (ribeirosantos2024tailoringendometrialcancer pages 1-2): Pedro Ribeiro-Santos, Carolina Martins Vieira, Gilson Gabriel Viana Veloso, Giovanna Vieira Giannecchini, Martina Parenza Arenhardt, Larissa Müller Gomes, Pedro Zanuncio, Flávio Silva Brandão, and Angélica Nogueira-Rodrigues. Tailoring endometrial cancer treatment based on molecular pathology: current status and possible impacts on systemic and local treatment. International Journal of Molecular Sciences, 25:7742, Jul 2024. URL: https://doi.org/10.3390/ijms25147742, doi:10.3390/ijms25147742. This article has 21 citations.

22. (tubridy2024treatmentofnodepositive pages 8-9): Elizabeth A. Tubridy, Neil K. Taunk, and Emily M. Ko. Treatment of node-positive endometrial cancer: chemotherapy, radiation, immunotherapy, and targeted therapy. Current Treatment Options in Oncology, 25:330-345, Jan 2024. URL: https://doi.org/10.1007/s11864-023-01169-x, doi:10.1007/s11864-023-01169-x. This article has 21 citations and is from a peer-reviewed journal.

23. (shim2024majorclinicalresearch pages 3-5): Seung-Hyuk Shim, Jung-Yun Lee, Yoo-Young Lee, Jeong-Yeol Park, Yong Jae Lee, Se Ik Kim, Gwan Hee Han, Eun Jung Yang, Joseph J Noh, Ga Won Yim, Joo-Hyuk Son, Nam Kyeong Kim, Tae-Hyun Kim, Tae-Wook Kong, Youn Jin Choi, Angela Cho, Hyunji Lim, Eun Bi Jang, Hyun Woong Cho, and Dong Hoon Suh. Major clinical research advances in gynecologic cancer in 2023: a tumultuous year for endometrial cancer. Journal of Gynecologic Oncology, Jan 2024. URL: https://doi.org/10.3802/jgo.2024.35.e66, doi:10.3802/jgo.2024.35.e66. This article has 9 citations and is from a peer-reviewed journal.

24. (luvero2024oldissuesand pages 5-6): Daniela Luvero, Gianna Barbara Cundari, Fernando Ficarola, Francesco Plotti, Corrado Terranova, Roberto Montera, Giorgio Bogani, Adele Silvagni, Federica Celoro, and Roberto Angioli. Old issues and new perspectives on endometrial cancer therapy: how molecular characteristics are changing the therapeutic pathway. Cancers, 16:1866, May 2024. URL: https://doi.org/10.3390/cancers16101866, doi:10.3390/cancers16101866. This article has 3 citations.

25. (ueda2024consistencybetweenprimary pages 1-2): Shoko Ueda, Tomohito Tanaka, Kensuke Hirosuna, Shunsuke Miyamoto, Hikaru Murakami, Ruri Nishie, Hiromitsu Tsuchihashi, Akihiko Toji, Natsuko Morita, Sousuke Hashida, Atsushi Daimon, Shinichi Terada, Hiroshi Maruoka, Yuhei Kogata, Kohei Taniguchi, Kazumasa Komura, and Masahide Ohmichi. Consistency between primary uterine corpus malignancies and their corresponding patient-derived xenograft models. International Journal of Molecular Sciences, 25:1486, Jan 2024. URL: https://doi.org/10.3390/ijms25031486, doi:10.3390/ijms25031486. This article has 0 citations.

26. (espedal2024mriradiomicscaptures pages 1-2): Heidi Espedal, Kristine E. Fasmer, Hege F. Berg, Jenny M. Lyngstad, Tomke Schilling, Camilla Krakstad, and Ingfrid S. Haldorsen. Mri radiomics captures early treatment response in patient-derived organoid endometrial cancer mouse models. Frontiers in Oncology, May 2024. URL: https://doi.org/10.3389/fonc.2024.1334541, doi:10.3389/fonc.2024.1334541. This article has 6 citations.

27. (yildiz2024murinexenograftmodels pages 17-19): Merve Yildiz, Andrea Romano, and Sofia Xanthoulea. Murine xenograft models as preclinical tools in endometrial cancer research. Cancers, 16:3994, Nov 2024. URL: https://doi.org/10.3390/cancers16233994, doi:10.3390/cancers16233994. This article has 1 citations.

28. (westin2024durvalumabpluscarboplatinpaclitaxel pages 2-4): Shannon N. Westin, Kathleen Moore, Hye Sook Chon, Jung-Yun Lee, Jessica Thomes Pepin, Michael Sundborg, Ayelet Shai, Joseph de la Garza, Shin Nishio, Michael A. Gold, Ke Wang, Kristi McIntyre, Todd D. Tillmanns, Stephanie V. Blank, Ji-Hong Liu, Michael McCollum, Fernando Contreras Mejia, Tadaaki Nishikawa, Kathryn Pennington, Zoltan Novak, Andreia Cristina De Melo, Jalid Sehouli, Dagmara Klasa-Mazurkiewicz, Christos Papadimitriou, Marta Gil-Martin, Birute Brasiuniene, Conor Donnelly, Paula Michelle del Rosario, Xiaochun Liu, Els Van Nieuwenhuysen, Sophia Frentzas, Kichendasse Ganessan, Bo Gao, Tarek Meniawy, Linda Mileshkin, Gary Richardson, Felicia Roncolato, Jean-Francois Baurain, Maryam Bourhaba, Eveline De Cuypere, Philip Debruyne, Hannelore Denys, Frederic Forget, Brigitte Honhon, Eric Joosens, Els Van Nieuwenhuysen, Vanessa da Costa Miranda, Andreia Cristina De Melo, Joao Daniel Guedes, Charles Andree Joseph de Padua, Nicolas Lazaretti, Carolina Martins Vieira, Andre Mattar, Daniela Neves Palmeiro, Christina Pimentel Oppermann Kussler, Pedro Emanuel Rubini Liedke, Joao Soares Nunes, Katsuki Arima Tiscoski, Allan Covens, Lara De Guerke, Prafull Ghatage, Lucy Gilbert, Susie Lau, Amit Oza, Diane Provencher, Omar Touhami, Li Congzhu, Wang Danbo, Lou Ge, Zhu Gen-Hai, Li Guiling, Shi Hong, Zheng Hong, Wen Hongwu, Liu Ji-Hong, Wang Jing, Wang Ke, Jiang Kui, Li Li, Wang Li, Hao Min, Zhou Qi, Gao Qinglei, Liao Sihai, Zhang Songling, Zhao Weidong, Xiaohua Wu, Wang Wuliang, Rutie Yin, Cheng Ying, Zhang Yu, Liang Zhiqing, Fernando Contreras Mejia, Angel Luis Hernandez, Carolina Ortiz Lopez, Carlos Javier Pacheco, Pedro Luis Ramos Guette, Jaime Rendon Pereira, Julian Rivera Diaz, Tomas Sanchez Villegas, Juan Pablo Suso, Marco Antonio Torregroza Otero, Karin Grisan, Elen Vettus, Bahriye Aktas, Eva Egger, Petra Krabisch, Andreas Muller, Joachim Rom, Jalid Sehouli, Antje Sperfeld, Pauline Wimberger, Andreas Zorr, George Fountzilas, Sofia Karageorgopoulou, Christos Papadimitriou, Amanda Psyrri, Florai Zagour, Karen Kar Loen Chan, Wing Ming Ho, Tibor Csoszi, Laszlo Landherr, Zoltan Novak, Zsuzsanna Papai, Robert Poka, Istvan Sipocz, Paul Devinder, Lovenish Goyal, Sudeep Gupta, Radheshyam Naik, Tushar Patil, S.P. Somashekhar, Ilan Bruchim, Svetlana Kovel, Anca Leibovici, Ora Rosengarten, Tamar Safra, Wataru Yamagami, Junzo Hamanishi, Yuichi Imai, Nobuhiro Kado, Shoji Kamiura, Hienori Kato, Eiji Kondo, Wataru Kudaka, Takashi Matsumoto, Masahiko Mori, Tadaaki Nishikawa, Shin Nishio, Aikou Okamoto, Mayu Yunokawa, Masayuki Sekine, Toshiyuki Sumi, Hirokuni Takano, Kazuhiro Takehara, Birute Brasiuniene, Arturas Inciura, Goda Jonuskiene, Jesus Elvis Cabrera Luviano, Adriana Dominguez-Andrade, Raquel Gerson-Cwilich, Carlos Hernandez Hernandez, Jesus Lopez Hernandez, Jose Luis Martinez Lira, Jaime Esteban Navarrete Aleman, Jessica Reyes Contreras, Vanessa Rosas Camargo, Wieslawa Bednarek, Dagmara Klasa-Mazurkiewicz, Tomasz Kubiatowski, Piotr Potemski, Magdalena Sikorska, Suk-Joon Chang, Sook Hee Hong, Sokbom Kang, Byoung-Gie Kim, Jan-Weon Kim, Yong Man Kim, Jung-Yun Lee, Sang Young Ryu, Yong Jung Song, Dmitriy Kirtbaya, Julya Kreynina, Alla Lisyanskaya, Yulia Makarova, Rashida Orlova, Albert Pirmagomedov, Valeria Saevets, Sufia Safina, Pavel Skopin, Alexandra Tyulyandina, Sheow Lei Lim, Lynette Ngo Su Mien, David Tan Shao Peng, Lay Tin Soh, Jesus Alarcon Company, Pilar Barretina, Purificacion Estevez-Garcia, Isaura Fernandez Perez, Fernando Galvez, Yolanda Garcia, Marta Gil-Martin, Jeronimo Martinez, Andres Redondo-Sanchez, Charles Anderson, Tara Berman, Stephanie Blank, William Bradley, James Burke, Fabio Cappuccini, Michael Carney, Setsuko Chambers, Lee-May Chen, Hye Sook Chon, Joseph de la Garza, Stephen Depasquale, Paul DiSilvestro, Babak Edraki, Evelyn Fleming, Jenny Fox, Michael Gold, Mary Gordinier, Michael Guy, Ellen Hartenbach, Chisten Haygood, Scott Jordan, Larry Kilgore, Young Kim, Joseph Lucci, Michael McCollum, Michael Mchale, Kristi McIntyre, Mark Messing, Eirwen Miller, Kathleen Moore, John Moroney, Michaela Onstad, Taylor Ortiz, Sobia Ozair, Kathryn Pennington, Krista Pfaendler, Anna Priebe, Terri Pustilnik, Kimberly Resnick, Peter Rose, Erin Salinas, Sudarshan Sharma, Urszula Sobol, Pamela Soliman, David Starks, Michael Sundborg, Eleonora Teplinsky, Jessica Thomes-Pepin, Todd Tillmanns, David Warshal, Shannon N. Westin, and Thomas Woliver. Durvalumab plus carboplatin/paclitaxel followed by maintenance durvalumab with or without olaparib as first-line treatment for advanced endometrial cancer: the phase iii duo-e trial. Journal of Clinical Oncology, 42:283-299, Jan 2024. URL: https://doi.org/10.1200/jco.23.02132, doi:10.1200/jco.23.02132. This article has 384 citations and is from a highest quality peer-reviewed journal.