The biological roles of CD47 in ovarian cancer progression.

Ovarian cancer is one of the most lethal malignant tumors, characterized by high incidence and poor prognosis. Patients relapse occurred in 65-80% after initial treatment. To date, no effective treatment has been established for these patients. Recently, CD47 has been considered as a promising immunotherapy target. In this paper, we reviewed the biological roles of CD47 in ovarian cancer and summarized the related mechanisms. For most types of cancers, the CD47/Sirpα immune checkpoint has attracted the most attention in immunotherapy. Notably, CD47 monoclonal antibodies and related molecules are promising in the immunotherapy of ovarian cancer, and further research is needed. In the future, new immunotherapy regimens targeting CD47 can be applied to the clinical treatment of ovarian cancer patients.

High-throughput viable circulating tumor cell isolation using tapered-slit membrane filter-based chipsets in the differential diagnosis of ovarian tumors.

OBJECTIVE: To evaluate the diagnostic performance of circulating tumor cells (CTCs) using tapered-slit membrane filter (TSF)-based chipsets for the differential diagnosis of adnexal tumors. METHODS: A total of 230 women with indeterminate adnexal tumors were prospectively enrolled. The sensitivity, specificity, and accuracy of the CTC-detecting chipsets were analyzed according to postoperative pathological results and compared with those of cancer antigen (CA)-125 and imaging tests. RESULTS: Eighty-one (40.3%) benign tumors, 31 (15.4%) borderline tumors, and 89 (44.3%) ovarian cancers were pathologically confirmed. The sensitivity, specificity, and accuracy of CTC-detecting chipsets (75.3%, 58.0%, and 67.1%) for differentiating ovarian cancer from benign tumors were similar to CA-125 (78.7%, 53.1%, and 66.5%), but lower than CT/MRI (94.2%, 77.9%, and 86.5%). "CTC or CA125" showed increased sensitivity (91.0%) and "CTC and CA-125" revealed increased specificity (77.8%), comparable to CT/MRI. CTC detection rates in stage I/II and stage III/IV ovarian cancers were 69.6% and 81.4%, respectively. The sensitivity to detect high-grade serous (HGS) cancer from benign tumors (84.6%) was higher than that to detect non-HGS cancers (68.0%). CONCLUSION: Although the diagnostic performance of the TSF platform to differentiate between ovarian cancer and benign tumors did not yield significant results, the combination of CTC and CA-125 showed promising potential in the diagnostic accuracy of ovarian cancer.

Integrin-linked kinase-frizzled 7 interaction maintains cancer stem cells to drive platinum resistance in ovarian cancer.

BACKGROUND: Platinum-based chemotherapy regimens are a mainstay in the management of ovarian cancer (OC), but emergence of chemoresistance poses a significant clinical challenge. The persistence of ovarian cancer stem cells (OCSCs) at the end of primary treatment contributes to disease recurrence. Here, we hypothesized that the extracellular matrix protects CSCs during chemotherapy and supports their tumorigenic functions by activating integrin-linked kinase (ILK), a key enzyme in drug resistance. METHODS: TCGA datasets and OC models were investigated using an integrated proteomic and gene expression analysis and examined ILK for correlations with chemoresistance pathways and clinical outcomes. Canonical Wnt pathway components, pro-survival signaling, and stemness were examined using OC models. To investigate the role of ILK in the OCSC-phenotype, a novel pharmacological inhibitor of ILK in combination with carboplatin was utilized in vitro and in vivo OC models. RESULTS: In response to increased fibronectin secretion and integrin ß1 clustering, aberrant ILK activation supported the OCSC phenotype, contributing to OC spheroid proliferation and reduced response to platinum treatment. Complexes formed by ILK with the Wnt receptor frizzled 7 (Fzd7) were detected in tumors and correlated with metastatic progression. Moreover, TCGA datasets confirmed that combined expression of ILK and Fzd7 in high grade serous ovarian tumors is correlated with reduced response to chemotherapy and poor patient outcomes. Mechanistically, interaction of ILK with Fzd7 increased the response to Wnt ligands, thereby amplifying the stemness-associated Wnt/ß-catenin signaling. Notably, preclinical studies showed that the novel ILK inhibitor compound 22 (cpd-22) alone disrupted ILK interaction with Fzd7 and CSC proliferation as spheroids. Furthermore, when combined with carboplatin, this disruption led to sustained AKT inhibition, apoptotic damage in OCSCs and reduced tumorigenicity in mice. CONCLUSIONS: This "outside-in" signaling mechanism is potentially actionable, and combined targeting of ILK-Fzd7 may lead to new therapeutic approaches to eradicate OCSCs and improve patient outcomes.

Metastatic malignant struma ovarii to the pituitary presenting as a sellar mass and responding to total thyroidectomy with adjuvant radioactive iodine therapy.

Malignant struma ovarii (MSO) is a rare ovarian teratoma composed primarily of thyroid tissue. Common sites of metastasis include peritoneum, bone, liver, lung, gastrointestinal tract and omentum. We present a woman in her 50s with a history of remote oophorectomy presenting with hypopituitarism and a 2.7 cm sellar mass. Trans-sphenoidal surgery for presumed pituitary macroadenoma achieved near total resection and resultant pathology surprisingly showed ectopic thyroid tissue. The patient acquired her ovarian pathology report from Southeast Asia which showed struma ovarii of the left ovary. The pituitary mass was thus determined to be a metastatic lesion from MSO. She underwent total thyroidectomy and radioactive iodine ablation therapy with good initial response and no regrowth of the tissue or emergence of distant metastases after 5 years of annual follow-up. To our knowledge, this is the first reported case of MSO to the pituitary.

The oncogenic roles of GPR176 in ovarian cancer: a molecular target for aggressiveness and gene therapy.

BACKGROUND: At present, the discovery of new biomarkers is of great significance for the early diagnosis, treatment and prognosis assessment of ovarian cancer. Previous findings indicated that aberrant G-protein-coupled receptor 176 (GPR176) expression might contribute to tumorigenesis and subsequent progression. However, the expression of GPR176 and the molecular mechanisms in ovarian cancer had not been investigated. METHODS: GPR176 expression was compared with clinicopathological features of ovarian cancer using immunohistochemical and bioinformatics analyses. GPR176-related genes and pathways were analysed using bioinformatics analysis. Additionally, the effects of GPR176 on ovarian cancer cell phenotypes were investigated. RESULTS: GPR176 expression positively correlated with elder age, clinicopathological staging, tumour residual status, and unfavourable survival of ovarian cancer, but negatively with purity loss, infiltration of B cells, and CD8+ T cells. Gene Set Enrichment Analysis showed that differential expression of GPR176 was involved in focal adhesion, ECM-receptor interaction, cell adhesion molecules and so on. STRING and Cytoscape were used to determine the top 10 nodes. Kyoto Encyclopaedia of Genes and Genomes analysis indicated that GPR176-related genes were involved in the ECM structural constituent and organisation and so on. GPR176 overexpression promoted the proliferation, anti-apoptosis, anti-pyroptosis, migration and invasion of ovarian cancer cells with overexpression of N-cadherin, Zeb1, Snail, Twist1, and under-expression of gasdermin D, caspase 1, and E-cadherin. CONCLUSION: GPR176 might be involved in the progression of ovarian cancer. It might be used as a biomarker to indicate the aggressive behaviour and poor prognosis of ovarian cancer and a target of genetic therapy.

Ovarian cancer is a gynecological cancer with high mortality. Due to the limited screening tests and treatments available, most ovarian cancer patients are diagnosed at a late stage and the prognosis is poor. The addition of new cancer diagnostic biomarkers and new intervention targets may improve quality of life and survival for patients with ovarian cancer. Previous studies have revealed the aberrant GPR176 expression might contribute to tumorigenesis and subsequent progression in many other tumours. In our study, GPR176 was found to promote the proliferation, anti-apoptosis, anti-pyroptosis, migration and invasion, EMT, and weakening the cellular adhesion of ovarian cancer cells, and involved in the Bcl-2/Bax or the PI3K/Akt/mTOR pathway. Therefore, abnormal expression of GPR176 might be served as a biomarker for aggressive behaviour and poor prognosis of ovarian cancer and a target for gene therapy.

Exploration and prognostic analysis of two types of high-risk ovarian cancers: clear cell vs. serous carcinoma: a population-based study.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) is a rare pathological histotype in ovarian cancer, while the survival rate of advanced OCCC (Stage III-IV) is substantially lower than that of the advanced serous ovarian cancer (OSC), which is the most common histotype. The goal of this study was to identify high-risk OCCC by comparing OSC and OCCC, with investigating potential risk and prognosis markers. METHODS: Patients diagnosed with ovarian cancer from 2009 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) Program. Logistic and Cox regression models were used to identify risk and prognostic factors in high-risk OCCC patients. Cancer-specific survival (CSS) and overall survival (OS) were assessed using Kaplan-Meier curves. Furthermore, Cox analysis was employed to build a nomogram model. The performance evaluation results were displayed using the C-index, calibration plots, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Immunohistochemically approach was used to identify the expression of the novel target (GPC3). RESULTS: In the Cox analysis for advanced OCCC, age (45-65 years), tumor numbers (total number of in situ/malignant tumors for patient), T3-stage, bilateral tumors, and liver metastases could be defined as prognostic variables. Nomogram showed good predictive power and clinical practicality. Compared with OSC, liver metastases had a stronger impact on the prognosis of patients with OCCC. T3-stage, positive distant lymph nodes metastases, and lung metastases were risk factors for developing liver metastases. Chemotherapy was an independent prognostic factor for patient with advanced OCCC, but had no effect on CSS in patients with liver metastases (p = 0.0656), while surgery was significantly related with better CSS in these patients (p < 0.0001) (p = 0.0041). GPC3 expression was detected in all tissue sections, and GPC3 staining was predominantly found in the cytoplasm and membranes. CONCLUSION: Advanced OCCC and OCCC with liver metastases are two types of high-risk OCCC. The constructed nomogram exhibited a satisfactory survival prediction for patients with advanced OCCC. GPC3 immunohistochemistry is expected to accumulate preclinical evidence to support the inclusion of GPC3 in OCCC targeted therapy.

Ovarian teratoma in a Swiss mountain dog.

A Swiss mountain dog, ~3 y old, was brought to a veterinary clinic because of a progressive enlargement of the abdomen. Upon clinical examination, a large mass was detected. After surgical extraction, the mass was confirmed to be a large ovarian teratoma. The weight of the tumor was > 16% of the dog's overall body weight. The dog recovered fully after surgery. The observations from this case suggest that, although teratomas are rare, prompt and accurate diagnosis is necessary to prevent further growth of these masses and to ensure positive outcomes.

Tératome ovarien chez un chien de montage suisse. Un chien de montagne suisse âgé d'environ 3 ans a été présenté dans une clinique vétérinaire en raison d'une augmentation de volume progressive de l'abdomen. Lors de l'examen clinique, une grosse masse a été détectée. À la suite du retrait chirurgical, la masse a été confirmée comme étant un large tératome ovarien. Le poids de la masse tumorale était > 16 % du poids total du chien. Le chien a récupéré complètement après la chirurgie. Les observations à partir de ce cas suggèrent, bien que les tératomes soient rares, un diagnostic rapide et exact est nécessaire pour prévenir une croissance ultérieure de ces masses et assurer une issue positive.(Traduit par Dr Serge Messier).

Molecular Pathology of Ovarian Epithelial Neoplasms: Predictive, Prognostic, and Emerging Biomarkers.

This review focuses on the diagnostic, prognostic, and predictive molecular biomarkers in ovarian epithelial neoplasms in the context of their morphologic classifications. Currently, most clinically actionable molecular findings are reported in high-grade serous carcinomas; however, the data on less common tumor types are rapidly accelerating. Overall, the advances in genomic knowledge over the last decade highlight the significance of integrating molecular findings with morphology in ovarian epithelial tumors for a wide-range of clinical applications, from assistance in diagnosis to predicting response to therapy.

Ovarian Cancer Diagnosis and Prognosis Based on Cell-Free DNA Methylation.

Background: Ovarian cancer stands as the deadliest malignant tumor within the female reproductive tract. As a result of the absence of effective diagnostic and monitoring markers, 75% of ovarian cancer cases are diagnosed at a late stage, leading to a mere 50% survival rate within five years. The advancement of molecular biology is essential for accurate diagnosis and treatment of ovarian cancer. Methods: A review of several randomized clinical trials, focusing on the ovarian cancer, was undertaken. The advancement of molecular biology and diagnostic methods related to accurate diagnosis and treatment of ovarian cancer were examined. Results: Liquid biopsy is an innovative method of detecting malignant tumors that has gained increasing attention over the past few years. Cell-free DNA assay-based liquid biopsies show potential in delineating tumor status heterogeneity and tracking tumor recurrence. DNA methylation influences a multitude of biological functions and diseases, especially during the initial phases of cancer. The cell-free DNA methylation profiling system has emerged as a sensitive and non-invasive technique for identifying and detecting the biological origins of cancer. It holds promise as a biomarker, enabling early screening, recurrence monitoring, and prognostic evaluation of cancer. Conclusions: This review evaluates recent advancements and challenges associated with cell-free DNA methylation analysis for the diagnosis, prognosis monitoring, and assessment of therapeutic responses in the management of ovarian cancers, aiming to offer guidance for precise diagnosis and treatment of this disease.

Ovarian cancer stands as the deadliest malignant tumor within the female reproductive tract. As a result of the absence of effective diagnostic and monitoring markers, 75% of ovarian cancer cases are diagnosed at a late stage, leading to a mere 50% survival rate within five years. Nearly 80% of advanced stages have a poor prognosis or recurrence within five years. Ovarian cancer is linked to a grim long-term prognosis attributable to its elevated mortality and recurrence rates. The advancement of molecular biology and diagnostic methods is essential for accurate diagnosis and treatment of ovarian cancer. Liquid biopsy is an innovative method of detecting malignant tumors that has gained increasing attention over the past few years. Cell-free DNA assay-based liquid biopsies show potential in delineating tumor status heterogeneity and tracking tumor recurrence. DNA methylation represents a prevalent epigenetic modification. DNA methylation influences a multitude of biological functions and diseases, especially during the initial phases of cancer. The cell-free DNA methylation profiling system has emerged as a sensitive and non-invasive technique for identifying and detecting the biological origins of cancer. This review assesses recent progress and obstacles linked to cell-free DNA methylation analysis for diagnosing, prognostic monitoring, and evaluating therapeutic responses in managing ovarian cancers.

Defining three ferroptosis-based molecular subtypes and developing a prognostic risk model for high-grade serous ovarian cancer.

BACKGROUND: As a newly defined regulated cell death, ferroptosis is a potential biomarker in ovarian cancer (OV). However, its underlying mechanism in tumor microenvironment (TME) and clinical prediction significance in OV remained to be elucidated. METHODS: The transcriptome data of high-grade serous OV from The Cancer Genome Atlas (TCGA) database were downloaded. Molecular subtypes were classified based on ferroptosis-correlated genes from the FerrDb database by performing consensus clustering analysis. The associations between the subtypes and clinicopathologic characteristics, mutation, regulatory pathways and immune landscape were assessed. A ferroptosis-related prognostic model was constructed and verified using International Cancer Genome Consortium (ICGC) cohort and GSE70769. RESULTS: Three molecular subtypes of OV were defined. Patients in subtype C3 tended to have the most favorable prognosis, while subtype C1 showing more mesenchymal cells, increased immune infiltration of Macrophages_M2, lower tumor purity, and epithelial-to-mesenchymal transition (EMT) features had the poorest prognosis. A ferroptosis-related risk model was constructed using 8 genes (PDP1, FCGBP, EPHA4, GAS1, SLC7A11, BLOC1S1, SPOCK2, and CXCL9) and manifested a strong prediction performance. High-risk patients had enriched EMT pathways, more Macrophages_M2, less plasma cells and CD8 cell infiltration, greater tendency of immune escape and worse prognosis. The risk score has negatively correlated relation with LAG3, TIGIT, CTLA4, IDO1, CD27, ICOS, and IL2RB but positively correlated with PVR, CD276, and CD28. Moreover, low-risk patients were more sensitive to Cisplatin and Gefitinib, Gemcitabine. CONCLUSIONS: Our results could improve the understanding of ferroptosis in OV, providing promising insights for the clinical targeted therapy for the cancer.

Rapid Progression of Malignant Peritoneal Mesothelioma Mimicking a Postoperative Complication in a Young Woman: A Case Report.

BACKGROUND Malignant peritoneal mesothelioma is a rare disease with a poor prognosis that often presents with vague symptoms and inconclusive laboratory test results. Causes include industrial pollutants, primarily asbestos, and certain genetic mutations, such as BAP1. Due to the nonspecific symptoms, it is often incidentally diagnosed during or after other surgical procedures. CASE REPORT A 35-year-old healthy woman underwent an uncomplicated laparoscopic left salpingo-oophorectomy for a symptomatic large ovarian mature cystic teratoma. She subsequently presented with late-onset postoperative fever, leukocytosis, and multiple intra-abdominal masses. Following an exploratory laparotomy, extensive infectious disease evaluation, and multiple biopsies requiring interdisciplinary collaboration, malignant peritoneal mesothelioma was diagnosed by positive histologic staining of an omental biopsy for D2-40 and CK5/6. This first specimen was positive for BAP1, with the second, a liver biopsy, testing negative for BAP1. The tumor cell testing was also notable for mutations in NF2, MLL2, and ARID1A, and the hereditary cancer genetic testing was overall unremarkable. Her disease progressed rapidly, and she died 6 months after her initial procedure. CONCLUSIONS This case of rapidly developing malignant peritoneal mesothelioma following surgical management of an ovarian mature teratoma highlights the complexity in diagnosing a rare disease that presents with nonspecific symptoms in an otherwise young and healthy woman. The rapid disease course was likely accelerated by expansive intraperitoneal spread and multiple somatic oncogenic mutations in BAP1, NF2, MLL2, and ARID1A. Gynecologists should keep a broad differential for postoperative complications, as occult malignancies can present with symptoms that mimic postoperative complications.

Epithelial ovarian cancer and brain metastases: might the BRCA status, PARP inhibitor administration, and surgical treatment impact the survival?

OBJECTIVE: To evaluate disease characteristics and survival according to BRCA status, administration of poly-(ADP-ribose) polymerase inhibitors (PARPi), and surgery in patients with ovarian cancer and brain metastases. METHODS: This is a monocentric retrospective cohort of patients with ovarian cancer and brain metastases treated between 2000 and 2021. Data were collected by a retrospective review of medical records and analyzed according to: (1) BRCA mutation; (2) PARPi before and after brain metastases; (3) surgery for brain metastases. RESULTS: Eighty-five patients with ovarian cancer and brain metastasis and known BRCA status (31 BRCA mutated (BRCAm), 54 BRCA wild-type (BRCAwt)) were analyzed. Twenty-two patients had received PARPi before brain metastases diagnosis (11 BRCAm, 11 BRCAwt) and 12 after (8 BRCAm, 4 BRCAwt). Brain metastases occurred >1 year later in patients who had received previous PARPi. Survival was longer in the BRCAm group (median post-brain metastasis survival: BRCAm 23 months vs BRCAwt 8 months, p=0.0015). No differences were found based on BRCA status analyzing the population who did not receive PARPi after brain metastasis (median post-brain metastasis survival: BRCAm 8 months vs BRCAwt 8 months, p=0.31). In the BRCAm group, survival was worse in patients who had received previous PARPi (median post-brain metastasis survival: PARPi before, 7 months vs no-PARPi before, 24 months, p=0.003). If PARPi was administered after brain metastases, survival of the overall population improved (median post-brain metastasis survival: PARPi after, 46 months vs no-PARPi after, 8 months, p=0.00038).In cases of surgery for brain metastases, the prognosis seemed better (median post-brain metastasis survival: surgery 13 months vs no-surgery 8 months, p=0.036). Three variables were significantly associated with prolonged survival at multivariate analysis: BRCA mutation, multimodal treatment, and ≤1 previous chemotherapy line. CONCLUSIONS: BRCA mutations might impact brain metastasis occurrence and lead to better outcomes. In a multimodal treatment, surgery seems to affect survival even in cases of extracranial disease. PARPi use should be considered as it seems to prolong survival if administered after brain metastasis.

Tumor microenvironment-induced FOXM1 regulates ovarian cancer stemness.

In ovarian tumors, the omental microenvironment profoundly influences the behavior of cancer cells and sustains the acquisition of stem-like traits, with major impacts on tumor aggressiveness and relapse. Here, we leverage a patient-derived platform of organotypic cultures to study the crosstalk between the tumor microenvironment and ovarian cancer stem cells. We discovered that the pro-tumorigenic transcription factor FOXM1 is specifically induced by the microenvironment in ovarian cancer stem cells, through activation of FAK/YAP signaling. The microenvironment-induced FOXM1 sustains stemness, and its inactivation reduces cancer stem cells survival in the omental niche and enhances their response to the PARP inhibitor Olaparib. By unveiling the novel role of FOXM1 in ovarian cancer stemness, our findings highlight patient-derived organotypic co-cultures as a powerful tool to capture clinically relevant mechanisms of the microenvironment/cancer stem cells crosstalk, contributing to the identification of tumor vulnerabilities.

Injectable bio-multifunctional hyaluronic acid-based hydrogels loaded with poly ADP-ribose polymerase inhibitors for ovarian cancer therapy.

The recent use of PARP inhibitors (PARPi) in the maintenance treatment of ovarian tumor has significantly improved the survival rates of cancer patients. However, the current oral administration of PARP inhibitors fails to realize optimal therapeutic effects due to the low bioavailability in cancerous tissues, and often leads to a range of systemic adverse effects including hematologic toxicities, digestive system reactions, and neurotoxicities. Therefore, the demand for an advanced drug delivery system that can ensure effective drug administration while minimizing these unfavorable reactions is pressing. Injectable hydrogel emerges as a promising solution for local administration with the capability of sustainable drug release. In this study, we developed an injectable hydrogel made from aminated hyaluronic acid and aldehyde-functionalized pluronic127 via Schiff base reaction. This hydrogel exhibits excellent injectability with short gelation time and remarkable self-healing ability, and is applied to load niraparib. The drug-loaded hydrogel (HP@Nir hydrogel) releases drugs sustainably as tested in vitro as well as displays significant anti-proliferation and anti-migratory properties on human epithelial ovarian cancer cell line. Notably, HP@Nir hydrogel effectively suppresses the growth of ovarian cancer, without significant adverse reactions as demonstrated in animal studies. Additionally, the developed hydrogel is gradually degraded in vivo for around 20 d, while maintaining good biocompatibility. Overall, the injectable hydrogel loaded with niraparib provides a secure and efficient strategy for the treatment and management of ovarian cancer.

Development and validation of radiomics nomogram for metastatic status of epithelial ovarian cancer.

To develop and validate an enhanced CT-based radiomics nomogram for evaluating preoperative metastasis risk of epithelial ovarian cancer (EOC). One hundred and nine patients with histologically confirmed EOC were retrospectively enrolled. The volume of interest (VOI) was delineated in preoperative enhanced CT images, and 851 radiomics features were extracted. The radiomics features were selected by the least absolute shrinkage and selection operator (LASSO), and the rad-score was calculated using the formula of the radiomics label. A clinical model, radiomics model, and combined model were constructed using the logistic regression classification algorithm. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were used to evaluate the diagnostic performance of the models. Seventy-five patients (68.8%) were histologically confirmed to have metastasis. Eleven optimal radiomics features were retained by the LASSO algorithm to develop the radiomic model. The combined model for evaluating metastasis of EOC achieved area under the curve (AUC) values of 0.929 (95% CI 0.8593-0.9996) in the training cohort and 0.909 (95% CI 0.7921-1.0000) in the test cohort. To facilitate clinical use, a radiomic nomogram was built by combining the clinical characteristics with rad-score. The DCA indicated that the nomogram had the most significant net benefit when the threshold probability exceeded 15%, surpassing the benefits of both the treat-all and treat-none strategies. Compared with clinical model and radiomics model, the radiomics nomogram has the best diagnostic performance in evaluating EOC metastasis. The nomogram is a useful and convenient tool for clinical doctors to develop personalized treatment plans for EOC patients.

12-O-deacetyl-phomoxanthone A inhibits ovarian tumor growth and metastasis by downregulating PDK4.

AIMS: The xanthone dimer 12-O-deacetyl-phomoxanthone A (12-ODPXA) was extracted from the secondary metabolites of the endophytic fungus Diaporthe goulteri. The 12-ODPXA compound exhibited anticancer properties in murine lymphoma; however, the anti-ovarian cancer (OC) mechanism has not yet been explored. Therefore, the present study evaluated whether 12-ODPXA reduces OC cell proliferation, metastasis, and invasion by downregulating pyruvate dehydrogenase kinase (PDK)4 expression. METHODS: Cell counting kit-8, colony formation, flow cytometry, wound healing, and transwell assays were performed to examine the effects of 12-ODPXA on OC cell proliferation, apoptosis, migration, and invasion. Transcriptome analysis was used to predict the changes in gene expression. Protein expression was determined using western blotting. Glucose, lactate, and adenosine triphosphate (ATP) test kits were used to measure glucose consumption and lactate and ATP production, respectively. Zebrafish xenograft models were constructed to elucidate the anti-OC effects of 12-ODPXA. RESULTS: The 12-ODPXA compound inhibited OC cell proliferation, migration, invasion, and glycolysis while inducing cell apoptosis via downregulation of PDK4. In vivo experiments showed that 12-ODPXA suppressed tumor growth and migration in zebrafish. CONCLUSION: Our data demonstrate that 12-ODPXA inhibits ovarian tumor growth and metastasis by downregulating PDK4, revealing the underlying mechanisms of action of 12-ODPXA in OC.

Targeting ferroptosis in ovarian cancer: Novel strategies to overcome chemotherapy resistance.

AIMS: This review investigates the role of ferroptosis in combating chemotherapy resistance in ovarian cancer, with a focus on its underlying mechanisms and therapeutic implications. MAIN METHODS: A database search was conducted up to December 2023 using PubMed, Scopus, Google Scholar, Web of Science, and the Cochrane Library. The keywords "ovarian cancer," "ferroptosis," "cisplatin," and "cisplatin resistance" were employed. We included studies that offered original data on the application of ferroptosis in platinum-based chemotherapy, focusing on both in-vitro and in-vivo research models. KEY FINDINGS: Our review reveals that ferroptosis significantly influences drug resistance in ovarian cancer. It investigates the existing studies to understand the role of ferroptosis in platinum resistance and explores its underlying mechanisms and assesses potential therapeutic strategies that uses ferroptosis to improve outcomes. The findings underscore the importance of ferroptosis in enhancing the effectiveness of platinum-based treatments and improving patient prognosis. SIGNIFICANCE: The potential of ferroptosis induction to develop novel therapeutic strategies against ovarian cancer, especially in cisplatin-resistant cases, is promising. The preliminary nature of these findings highlights the necessity for further research to bring these insights into clinical practice. This would not only improve treatment outcomes and prognosis but also encourage ongoing studies into ferroptosis as a viable therapeutic approach.