Search Results (740)

Objective: The primary objective of this systematic review is to present current knowledge about the oncobiome of gynecological cancers. Methods: Our systematic review contains data about the oncobiome of uterine corpus cancer, ovarian cancer and cervical cancer. Articles about other gynecological cancers were excluded. Results: A total of 72 articles were included in our systematic review. In uterine corpus cancer, cervical cancer and ovarian cancer, representatives of bacteria, fungi, viruses and parasites can be found. The oncobiome of ovarian cancer is connected with the oncobiome of head and neck cancers. Our systematic review proved that the human papilloma virus is connected with ovarian and cervical cancer. Gut dysbiosis can be used as a marker of ovarian cancer. In cervical cancer, we found the difference between the microbiota of healthy patients and patients with cervical cancer. Methylobacter, Robignitomaculum, Klebsiella, Micromonospora and Microbispora have an impact on overall survival. The microbiome of uterine corpus cancer is more differentiated than in cancer-free samples. Chronic endometrial inflammation has an impact on endometrial microbiome. Discussion: Treatment of gynecological cancers is changing permanently. Chemotherapy, as a systematic treatment, is being left in the past. Modern methods of therapy are addressed to specific genes. In the past, researchers claimed that tumors are sterile. However, the newest research indicates that malignancies were found to have genetic fragments of pathogens, which can be used as vectors for medications or as markers for the detection of a specific malignancy. Three most common gynecological cancers are as follows: endometrial cancer, ovarian cancer and cervical cancer. Each of these has their specific microbiome, which can be used for oncological treatment. These discoveries create possibilities for new, efficient methods of treatment. This systematic review analyzes publications about the composition of the gynecological tumor microenvironment, correlation between microbiomes of different organs, the female reproductive tract and the microbiome of the female reproductive tract during malignancy. Moreover, we provide information on the influence of some pathogens on the treatment. Full article

Peritoneal carcinomatosis (PC) and malignant pleural effusions (MPE) are two common complications of cancers metastatic to the respective body cavities. A PC diagnosis indicates metastasis to the tissue lining the abdominal cavity and is most common in patients with gastrointestinal and gynecological cancers. It is often accompanied by ascites, an accumulation of serous fluid in the abdomen. MPE presents as the accumulation of fluid in the space between the lungs and chest wall. It is a common terminal event in patients diagnosed with breast cancer, lung cancer, lymphoma, and mesothelial cancers, and less commonly, in a wide variety of other epithelial cancers. Due to the aggressive nature of cavitary tumors, the outcome of current treatments for both PC and MPE remains bleak. Although PC and MPE are characteristically affected by different sets of primary tumors (lung/breast/mesothelioma for MPE and gynecologic/gastrointestinal for PC), their environments share common cytokines and cellular components. Owing to the unique cytokine and chemokine content, this environment promotes aggressive tumor behavior and paradoxically both recruits and suppresses central memory and effector memory T cells. The cellular and secretomic complexity of the cavitary tumor environment renders most currently available therapeutics ineffective but also invites approaches that leverage the robust T-cell infiltrate while addressing the causes of local suppression of anti-tumor immunity. Interactions between the heterogeneous components of the tumor environment are an area of active research. We highlight the roles of the immune cell infiltrate, stromal cells, and tumor cells, and the soluble products that they secrete into their environment. A more comprehensive understanding of the cavitary tumor environment can be expected to lead to better immunotherapeutic approaches to these devastating conditions. Full article

Ovarian cancer (OCa) remains the most lethal gynecologic malignancy in the United States, with low-grade serous and mucinous subtypes frequently driven by KRAS mutations. These mutations activate downstream MAPK and PI3K/AKT signaling pathways, contributing to tumor progression and resistance to therapy. Although the MEK inhibitor trametinib is used to target these pathways, its efficacy is limited in KRAS-mutant OCa due to compensatory activation of the leukemia inhibitory factor (LIF)/LIF receptor (LIFR) axis. In this study, we evaluated the therapeutic potential of combining trametinib with EC359, a selective LIFR inhibitor, in Ras/Raf-driven OCa models. EC359 significantly reduced cell viability, clonogenic survival, and induced cell death via ferroptosis in vitro. Mechanistic studies revealed that EC359 suppressed trametinib-induced activation of LIFR downstream signaling. RNA-seq analysis showed that combination therapy downregulated mitochondrial translation and MYC target genes while upregulating apoptosis-related genes. In vivo, EC359 and trametinib co-treatment significantly reduced tumor growth in xenograft and PDX models without inducing toxicity. Our studies identify LIFR signaling as a critical vulnerability in Ras/Raf-mutant and low grade serous OCa. Further, it provides strong preclinical rationale for EC359 and trametinib combination therapy as a new therapeutic strategy for treating Ras/Raf-driven OCa and low-grade serous OCa. Full article

Primary ovarian large cell neuroendocrine carcinoma is an extremely rare and aggressive gynecologic malignancy with poorly defined molecular characteristics and no standard treatment protocols. We present a case of pure ovarian LCNEC in a postmenopausal woman who underwent optimal cytoreductive surgery followed by platinum-based chemotherapy. Histopathologic and immunohistochemical analyses confirmed the diagnosis. Next-generation sequencing (NGS) revealed a pathogenic BRCA2 frameshift mutation (c.7177dupA), an ATM nonsense mutation, and Tier II mutations in TP53 and PTEN. The tumor exhibited homologous recombination deficiency (HRD), microsatellite instability-high (MSI-H), and an exceptionally high tumor mutational burden (TMB) of 277.49 mutations/Mb. These molecular alterations closely resemble those observed in high-grade neuroendocrine carcinomas of cervical and endometrial origin, suggesting a convergent genomic profile across gynecologic neuroendocrine carcinomas (NECs). Our findings underscore the potential of comprehensive genomic profiling in rare tumors such as ovarian LCNEC to refine diagnosis and identify candidates for biomarker-driven therapies, including PARP inhibitors and immune checkpoint inhibitors. This case supports the integration of molecular diagnostics into clinical practice and highlights the need for prospective studies incorporating molecular stratification to inform treatment strategies for rare and aggressive neuroendocrine tumors. Full article

Guidelines on fertility preservation (FP) have been developed to help young women preserve their fertility, which may have been impaired due to cancer. Nevertheless, the correct management of oncological patients of childbearing age remains controversial, especially regarding gynecological malignancies. For this reason, we explored the current knowledge, attitudes, and clinical practices of physicians towards the challenges of FP in this population. A specially developed questionnaire on fertility-related issues in patients with gynecological cancer was administered via email to 167 people, representing 167 centers of the Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) group. A total of 56 physicians, who represented 56 out of these 167 centers, responded to our survey (response rate: 33.5%). Approximately half of these physicians stated that they had adequate knowledge about the use of gonadotropin-releasing analog (GnRHa) injections (n = 30; 53.6%), the cryopreservation of oocytes (n = 25; 44.6%), and the cryopreservation of ovarian tissue (n = 27; 48.2%) in patients with gynecological tumors. Meanwhile, regarding (borderline) ovarian tumors, endometrial or cervical cancer, and genetic mutation carriers, attitudes varied substantially. In conclusion, the results of our survey highlight the different perspectives on controversial topics among physicians directly involved in the treatment of these tumors. These findings also demonstrate the lack of evidence on these issues to adequately counsel this specific patient population. Full article

Epithelial ovarian cancer (EOC) remains one of the deadliest gynecologic malignancies, largely due to late diagnosis and treatment resistance. The main objective of this study is to identify and validate CDK1 as a high-confidence therapeutic target in EOC and to assess the dual-target inhibitory potential of the natural compound Naringin against both CDK1 and its regulator WEE1. This study employed an integrative pipeline combining transcriptomic profiling, protein–protein interaction network analysis, machine learning, and molecular simulations to identify key oncogenic regulators in EOC. CDK1 emerged as a central hub gene, exhibiting strong association with poor prognosis and signaling convergence. CDK1 overexpression correlated with adverse survival outcomes and robust involvement in critical oncogenic pathways. Molecular docking and dynamics simulations assessed the binding efficacy of seven compounds with CDK1 and WEE1, with Naringin showing high-affinity binding, stable complex formation, and minimal predicted toxicity. This study underscores the power of computational-experimental integration in accelerating oncology drug discovery, providing visual and quantitative evidence that systematically connect the study’s aim to its findings. Full article

Introduction: Pelvic exenteration (PEx) was first described in the 1940s as a palliative procedure in managing cervical cancer. Since then, advancements in perioperative care have transformed the options available to patients. This highly morbid procedure now offers a “cure” in a select cohort of patients with locally advanced and recurrent pelvic cancers. The large volume of literature in this field has resulted in a heterogeneity of data reporting, making comparative analysis extremely difficult. As such, we set out to examine the current literature and identify currently reported outcomes to guide development of a core information set (CIS) for data reporting for PEx in non-rectal cancers. Methods: A systematic review was carried out. Studies reporting on outcomes following PEx for advanced and recurrent gynecological, urological, and other non-rectal malignancies were included. Standardized outcomes were extracted and mapped to pre-determined domains. Results: Forty-four studies were found to meet our inclusion criteria. A total of 1735 data elements (DEs) were extracted verbatim, and these were assimilated into 111 standard DEs across nine domains. A wide range of reporting frequencies was observed, with the pathological domain containing the highest overall frequencies of DE reporting. Conversely, patient-reported and functional outcomes were noted to be the domain with the lowest frequency. Conclusions: This review highlights recent trends of increased reporting in the field of PEx and how this had invariably resulted in heterogeneous data reporting. We aim to guide the development of a CIS for reporting in non-rectal pelvic malignancies to help standardize future reporting. Full article

Cervical cancer remains the fourth most common malignancy among women worldwide, with over 600,000 new cases and approximately 350,000 deaths in 2022. Lymph node (LN) status is a critical prognostic factor, and in 2018, the International Federation of Gynecology and Obstetrics (FIGO) revised its staging system to include regional LN metastases, underscoring the importance of accurate nodal assessment. Sentinel lymph node biopsy (SLNB) has emerged as a minimally invasive alternative to systematic pelvic lymphadenectomy in early-stage disease, aiming to shorten operative time, reduce healthcare costs, and minimize treatment-related morbidity. This review synthesizes current evidence on SLNB in early-stage cervical cancer, including its diagnostic accuracy, optimal techniques, cost-effectiveness, and remaining clinical challenges. Data from prospective trials and meta-analyses demonstrate that SLNB provides high detection rates, especially with bilateral mapping and the use of advanced tracers such as indocyanine green. Ultrastaging further improves the detection of micrometastases and isolated tumor cells, refining adjuvant therapy decisions. Compared to full lymphadenectomy, SLNB significantly decreases intraoperative blood loss, operative time, and postoperative complications—most notably, lymphedema—while maintaining equivalent disease-free and overall survival. International guidelines now endorse SLNB for appropriately selected patients with early-stage cervical cancer (tumor size < 4 cm, negative preoperative imaging). However, variations persist between European and U.S. recommendations regarding its role as a standalone procedure. Future research must address protocol standardization, the prognostic relevance of low-volume metastases, and factors influencing mapping success. Overall, SLNB represents a paradigm shift toward more individualized, evidence-based surgical management of early-stage cervical cancer. Full article

Background: Endometrial cancer (EC) is one of the most common gynecologic malignancies, with a rising incidence worldwide. The Cancer Genome Atlas (TCGA) classifies EC into four molecular subtypes, among which the high-copy number subtype is characterized by TP53 mutations and associated with poor prognosis. However, this subtype remains understudied. IL4I1, an immunoregulatory enzyme implicated in various cancers, has emerged as a potential biomarker for tumor progression. This study aimed to explore IL4I1 as a prognostic marker in P53-mutant EC and to identify its potential as a therapeutic target. Methods: We retrospectively analyzed clinical data from 495 EC patients and selected 33 P53-mutant cases using Sanger sequencing and immunohistochemistry. Tumor tissues were collected via laser capture microdissection, stratified by five-year survival outcomes. IL4I1 expression was assessed through 4D label-free proteomics, immunohistochemistry, and Western blotting. TCGA data were used to validate expression patterns and prognostic significance. Functional analyses were performed using IL4I1-knockout P53-mutant EC cell lines generated via CRISPR/Cas9, followed by phenotypic assays and xenograft models. Results: IL4I1 was significantly upregulated in deceased patients and correlated with immune microenvironment alterations in TCGA data. Knockout of IL4I1 inhibited proliferation, migration, and invasion in vitro and tumor growth in vivo. Conclusions: IL4I1 is a key player in the aggressiveness of P53-mutant EC. It holds promise as a prognostic biomarker and may serve as a novel target for precision therapies in this high-risk EC subtype. Full article

Primary Fallopian tube carcinomas (PFTCs) are rare malignancies that are often misclassified as ovarian cancers due to overlapping clinical and pathological features. This frequent misdiagnosis contributes to the under-recognition of PFTCs, which account for a larger proportion of pelvic malignancies than historically reported. The central aim of this literature review is to highlight the critical importance of and methods for achieving an early diagnosis of Fallopian tube cancer, to improve patient outcomes. We classify benign and malignant fallopian tube neoplasms and evaluate the essential role of clinical evaluation and advanced imaging techniques, considering especially ultrasound, MRI, and PET-CT, in achieving an accurate and timely diagnosis. While histopathology remains the gold standard, imaging is pivotal for differentiating benign from malignant tubal lesions. This review details clinical manifestations, diagnostic pitfalls, and the necessity of a multidisciplinary approach to management. We conclude that advancing early detection through refined diagnostic criteria is essential to guiding effective, patient-specific therapeutic interventions. Full article

Cervical cancer is a major gynecological malignancy linked to hormonal dysregulation and genetic alterations. Chemotherapy is standard but limited by toxicity and chemoresistance, prompting interest in plant-derived adjuncts. This study examined the anticancer and immunomodulatory effects of Hesperidin (Hes), a citrus flavonoid, with Doxorubicin (DX) in HeLa cervical cancer cells. Cell viability was assessed by MTT assay, apoptotic markers (Bcl-2, Caspase-3) by RT-qPCR, and inflammatory cytokines (IL-1β, IL-6, TNF-α, IFN-γ) by ELISA. Cytokine levels were normalized to 10⁴ viable cells, and mRNA expression of all four cytokines was quantified by RT-qPCR, confirming protein-level changes and showing the strongest IL-6 suppression with Hes+DX. Chou–Talalay combination index (CI) analysis demonstrated synergistic interactions (CI < 1.0) between Hes and DX across all tested concentrations, with strong synergism (CI < 0.7) at medium and high doses, particularly at 48 and 72 h. Hes alone showed dose-dependent cytotoxicity, while the combination markedly increased Caspase-3, reduced Bcl-2, and decreased IL-1β, IL-6, and TNF-α, indicating enhanced intrinsic apoptosis and complementary immunomodulation. These results suggest that Hes augments DX’s pro-apoptotic and anti-inflammatory effects, potentially allowing lower chemotherapy doses and reduced systemic toxicity in cervical cancer treatment. Full article

Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries, and its incidence is increasing globally. While early-stage ECs generally show good prognosis, advanced or recurrent cases and those with aggressive histologic subtypes exhibit poor outcomes. Traditional histopathologic classification, however, fails to reflect the molecular heterogeneity of EC, limiting its role in guiding treatment. Recent developments in multi-omics have enhanced our understanding of EC biology, which supports more personalized treatment strategies. The Cancer Genome Atlas (TCGA) classification has provided a more systematic molecular framework for stratifying risk and identifying prognostic and therapeutic biomarkers. This review discusses the latest developments in multi-omics-based classification of EC, highlights emerging diagnostic and therapeutic strategies, and summarizes ongoing clinical trials that aim to translate molecular discoveries into improved outcomes. Full article

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, often diagnosed at an advanced stage due to its asymptomatic progression. The high recurrence rate and development of platinum-based chemotherapy resistance contribute to its poor prognosis. Despite advancements in molecular profiling, predictive biomarkers for chemotherapy response and recurrence risk remain limited. In this study, we developed OvarianTag™, a biomarker panel integrating apoptosis and necroptosis pathways, to predict chemotherapy benefit and disease progression in EOC patients. This observational study was conducted in two phases. In the first phase, 45 patients were recruited, and RNA was extracted from fresh ovarian tissues (normal, benign, and malignant). qRT-PCR was performed to assess the relative expression of genes involved in apoptosis and necroptosis-regulated cell death pathways. Machine learning algorithms were applied to identify the relevant prognostic markers, leading to the development of OvarianTag™. In the second phase, 55 additional EOC patients were included, and their formalin-fixed, paraffin-embedded (FFPE) tumor samples were analyzed using qRT-PCR. The classifier algorithm incorporated hierarchical clustering to stratify patients based on gene expression profiles. Significant differences in TNFRSF10C/TRAIL-R3, TNFRSF10B/TRAIL-R2, and CASP8 expression levels were observed between patient groups. CASP8 downregulation was strongly correlated with platinum resistance and a poor prognosis. Decision tree models achieved 83.3% accuracy in predicting platinum response and 79.2% accuracy in recurrence risk stratification. The OvarianTag™ classifier demonstrated high sensitivity and specificity in identifying high-risk patients, supporting its potential as a prognostic tool. The OvarianTag™ panel provides a novel approach for risk stratification in EOC, integrating apoptosis and necroptosis pathways to refine chemotherapy response prediction and recurrence risk assessment. This molecular assay has the potential to guide personalized treatment strategies, enhancing clinical decision-making and improving patient outcomes. Further validation in independent cohorts is warranted to establish its clinical utility. Full article

Zonula occludens-1 (ZO-1), encoded by the TJP1 gene, is a crucial scaffolding protein within tight junctions that maintains epithelial and endothelial barrier integrity. In addition to its structural role, ZO-1 participates in signal transduction pathways that influence various cellular processes such as proliferation, differentiation, and apoptosis. Increasing evidence suggests that tight junction proteins, including ZO-1, play important regulatory roles in tumor progression, particularly by modulating metastasis, cell polarity, and vascular remodeling. Ovarian cancer, the most lethal gynecologic malignancy, is characterized by rapid growth, peritoneal dissemination, and a strong reliance on tumor angiogenesis. However, the specific role of ZO-1 in regulating angiogenesis within ovarian cancer remains poorly defined. In this study, we used CRISPR-Cas9-mediated gene editing to generate TJP1 knockout (KO) ovarian cancer cell lines and investigated the impact of ZO-1 loss on the expression of angiogenesis-related genes. Transcriptomic and qRT-PCR analyses revealed upregulation of KLF5 and IL-8, both of which are well-established pro-angiogenic factors. Furthermore, functional assessment using a Matrigel™ tube formation assay demonstrated that conditioned media from ZO-1-deficient cells significantly enhanced endothelial tube formation. These findings indicate that ZO-1 loss promotes a pro-angiogenic tumor microenvironment, likely through modulation of key signaling molecules such as KLF5 and IL-8. Therefore, ZO-1 may serve as a potential suppressor of angiogenesis and a therapeutic target in ovarian cancer. Full article