levated levels of cancer antigen-125 (CA-125) are strongly associated with the likelihood of ovarian cancer recurrence, making it a significant concern in clinical practice. [18F]FDG PET/CT has emerged as a valuable tool for detecting recurrent ovarian cancer. This study aims to evaluate the diagnostic performance of [18F]FDG PET/CT in identifying ovarian cancer relapse among patients exhibiting rising CA-125 levels, through a systematic review and meta-analysis. A comprehensive search was carried out across PubMed, Embase, and the Cochrane Library, encompassing all records up to July 2024. Studies were eligible for inclusion if they provided data on true positives (TP), false positives (FP), true negatives (TN), and false negatives (FN) regarding the detection of ovarian cancer recurrence in patients with elevated CA-125 levels. Studies were excluded if they were duplicates, lacked full-text availability, contained incomplete information or were unable to be included in data extraction, involved animal studies, or were reviews or systematic reviews. The data were analyzed using STATA version 15.1. Across all included studies, the pooled sensitivity and specificity were 0.94 (95% confidence interval (CI): 0.89-0.97) and 0.89 (95% CI: 0.71-0.96), respectively. The positive likelihood ratio (LR+) was 7.11 (95% CI: 2.75-18.38), while the negative likelihood ratio (LR-) was 0.07 (95% CI: 0.03-0.15). The overall diagnostic odds ratio (DOR) amounted to 99.20 (95% CI: 26.66-369.14). Additionally, the area under the receiver operating characteristic curve (AUC) reached 0.97 (95% CI: 0.95-0.98). With its high sensitivity and specificity, [18F]FDG PET/CT serves as an effective tool for detecting ovarian cancer recurrence in patients exhibiting elevated CA-125 levels. These results endorse its effectiveness as a dependable diagnostic method in clinical settings. This meta-analysis provides updated pooled evidence that [18F]FDG PET/CT demonstrates excellent diagnostic accuracy (AUC 0.97) in detecting ovarian cancer recurrence in patients with elevated CA-125. Compared with earlier meta-analyses limited to PET alone, our findings highlight the added value of integrated PET/CT systems in improving specificity and reducing false positives, thereby supporting its recommendation in international guidelines and strengthening its role in clinical decision-making for recurrent ovarian cancer.

Ovarian cancer remains the most lethal gynecologic malignancy, due in part to the establishment of a profoundly immunosuppressive tumor microenvironment (TME). While toll-like receptor 5 (TLR5) signaling has previously been implicated in promoting myeloid cell recruitment to the ovarian TME, source(s) of ligand and systemic effects on hematopoiesis remain poorly understood. Here, we demonstrate that ovarian cancer disrupts gut barrier integrity, leading to systemic translocation of TLR5 ligands into the peritoneum, blood, and bone marrow. This translocation correlates with enhanced expansion of myeloid progenitors in the bone marrow of wild-type (WT) but not TLR5-deficient (TLR5 KO) mice, leading to enhanced accumulation of monocytes and macrophages into the TME. In the bone marrow, direct TLR5 signaling induced expansion of TLR5-expressing granulocyte-monocyte progenitors, a phenotype recapitulated both using an in vitro colony-forming assay and in a mixed bone marrow chimera model. Acute pharmacologic blockade of TLR5 in tumor-bearing mice altered the composition of tumor-associated myeloid populations, reducing the frequency of monocytes and CCR2-expressing macrophages accumulating within the TME of WT mice. These data reveal that chronic TLR5 signaling, driven by tumor-induced loss of gut barrier integrity, promotes expansion of myeloid cells within the bone marrow and is a host-intrinsic mechanism driving accumulation of immature monocytes and macrophages into the TME.

The rate of kidney transplantation has been steadily increasing worldwide, accompanied by significant improvements in post-transplant survival rates. However, transplant recipients have a higher incidence of malignancies compared with the general population, and their oncological management often poses unique challenges. In recent years, major advances in the treatment of ovarian cancer have expanded the therapeutic options available for recurrent disease. Two randomised trials have underscored the role of surgery in platinum-sensitive recurrent ovarian cancer while minimally invasive approaches have demonstrated reduced morbidity without compromising oncologic outcomes in carefully selected patients. For frail and immunosuppressed individuals, the minimally invasive approach may offer substantial advantages- including fewer wound complications, shorter hospitalisation, and earlier resumption of oral intake and immunosuppressive therapy. Despite these potential benefits, evidence regarding the feasibility and safety of minimally invasive secondary cytoreduction in kidney-transplanted patients remains limited. To demonstrate the feasibility and outcomes of robotic surgery in a platinum-sensitive ovarian cancer (OC) recurrence in a frail, kidney-transplant patient. A woman in her 50s with a history of kidney transplantation presented with isolated pelvic high-grade serous OC recurrence. Positron emission tomography scan revealed a 15 mm solid lesion with increased uptake infiltrating the rectum. A robot-assisted rectal resection was performed using the Da Vinci Xi Surgical System. The approach included four 8 mm robotic trocars: trans umbilical optical port, right and left iliac fossa, suprapubic region, and one 10 mm laparoscopic port at the left Palmer's point. Colorectal anastomosis was completed using the Ethicon Endo-Surgery 60 mm stapler by a specialised peritoneal and retroperitoneal team. R0 resection was achieved with no complications or delays in immunosuppressive therapy resumption; final histology confirmed rectal involvement, and adjuvant chemotherapy was promptly initiated. At the two-year follow-up, the patient was disease-free. This case supports minimally invasive surgery as a valid approach in selected, frail, immunosuppressed patients with isolated OC recurrence.

Background: Obesity and modifiable lifestyle factors contribute significantly to the rising global burden of cancer, particularly gynecologic malignancies such as endometrial and ovarian cancer. Despite strong biological plausibility, the role of lifestyle interventions in improving outcomes for women with gynecologic cancers remains underexplored. Objective: This review synthesizes current evidence on the impact of dietary and physical activity interventions on gynecologic cancer outcomes, highlighting links and existing clinical guidelines. Methods: Literature exploring the influence of obesity, inflammation hormonal dysregulation, insulin resistance, and gut microbiome alterations on cancer progression were assessed, and studies assessing the effects of lifestyle interventions in gynecologic cancers were explored. Results: Obesity-induced inflammation and hormonal imbalances are key drivers of tumorigenesis. Structured exercise and adherence to anti-inflammatory diets, such as the Mediterranean diet, can reduce pro-inflammatory cytokines, improve insulin sensitivity, regulate estrogen metabolism, and enhance immune function. These interventions also modulate angiogenesis and promote a favorable gut microbiome, offering a biologically plausible approach to slowing cancer progression. Conclusion: Diet and exercise represent promising, low-risk strategies to improve quality of life and potentially enhance survival in women with gynecologic cancers. Greater integration of lifestyle interventions into gynecologic oncology care is warranted, guided by evidence and recommendations from national cancer organizations.

Development of female non-hormonal contraceptives (NHCs) is a laudable goal because hormonal (steroidal) contraceptives are either contraindicated or not well tolerated by a substantial proportion of women. Whereas currently available hormonal contraceptives for women have their drawbacks, they do have some benefits that we should strive to preserve in NHCs. For example, combination oral birth control pills reduce the risks of some benign and malignant gynecological pathologies, such as ovarian and endometrial cancer. Regardless of whether NHCs work by preventing ovulation or fertilization, they risk losing some of the non-contraceptive benefits of hormonal contraceptives if not designed with great care. I assert that female NHCs should be designed to preserve, or at least not negate, the ovarian and endometrial cancer risk reductions conferred by some hormonal methods.

Longitudinal data are often available in cohort studies and clinical settings, such as covariates collected at cohort follow-up visits or prescriptions captured in electronic health records. Such longitudinal information, if correlates with the health event of interest, may be incorporated to dynamically predict the probability of a health event with better precision. Landmarking is a popular approach to dynamic prediction. There are well-established methods for landmarking using full cohort data, but collecting data on all cohort members may not be feasible when resource is limited. Instead, one may select a subset of the cohort using subsampling designs, and only collect data on this subset. In this work, we present conditional likelihood and inverse-probability weighted methods for landmarking using data from cohort subsampling designs, and discuss considerations for choosing a particular method. Simulations are conducted to evaluate the applicability of the methods and their predictive performance in different scenarios. Results show that our methods have similar predictive performance to the full cohort analysis but only use small fractions of the full cohort data. We use real nested case-control data from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial to illustrate the methods.

Testing for germline BRCA (gBRCA) mutations in patients with HER2-negative early breast cancer soon after diagnosis and before surgery (early testing) can influence surgical decisions, targeted adjuvant treatment access, and preventative care for relatives. The objective of this study was to identify evidence gaps in economic analyses of gBRCA testing in breast cancer. We conducted a targeted literature review using MEDLINE to identify cost-effectiveness analyses (CEAs) of gBRCA testing in patients with breast or ovarian cancer published January 2014-April 2024. Ovarian cancer models were included given that gBRCA status also impacts treatment and family member decisions. To evaluate the comprehensiveness of these studies, we mapped components against value elements relevant to genetic testing, synthesized from published frameworks and literature. A total of 26 CEAs of gBRCA testing were identified. Most studies (n = 17) assumed gBRCA testing increased risk-reducing surgeries (RRS), eight assumed gBRCA testing would guide poly adenosine diphosphate-ribose polymerase inhibitor (PARPi) use, and only one considered both. None assessed the value of early vs. late testing. We identified 21 value elements relevant to genetic testing; 15 CEAs included cascade testing, five included work productivity, and two included patient costs. When comparing gBRCA testing to no testing (n = 19), most studies concluded testing was cost-effective (n = 14). No CEAs have assessed the value of early gBRCA testing or comprehensively modeled downstream impacts to RRS and PARPi use with consideration for broader value elements. Further studies are needed to assess the full value of early gBRCA testing strategies.

Ovarian cancer (OC) remains a highly lethal gynecologic malignancy characterized by substantial molecular heterogeneity and diagnostic challenges. Although many reviews examine specific aspects of OC biology or treatment, few attempt to connect recent findings into a broader and coherent picture. This review provides an integrated and forward-looking synthesis of emerging mechanisms and therapeutic trends in OC, understanding OC progression and therapeutic resistance. Unique contributions of this review include providing a unified interpretation of emerging multi-omics evidence that reshapes the biological understanding of individual OC histotypes, delineating key metabolic dependencies such as glutamine addiction, aberrant lipid remodeling, glycolytic plasticity and purine pathway rewiring as potential therapeutic entry points, and elucidating how ascites-driven immune dysfunction remodels antitumor immunity to ultimately influence the effectiveness of cancer vaccines, immune checkpoint blockade and adoptive cell transfer therapies. Additionally, the review articulates underexplored therapeutic intersections, including nanotechnology-enhanced immunotherapy, gene-editing nanocarriers, and microbiome-mediated modulation of drug sensitivity and immune activation. By integrating these diverse yet interconnected domains, this review proposes updated conceptual models and cross-therapeutic strategies aimed at overcoming chemoresistance and advancing precision, personalized treatment paradigms in OC.

Increasing estrogen levels beyond the normal limit can be an indicator of a serious health problem which can be the cause of fibrosis or tumor development in the ovary tissue. In the current study, we seek to understand the mechanism of estrogen and whether the exposure of estradiol and phytoestrogens together increases the risk of developing ovarian cancer. Here, we used 32 healthy adult female rats. They were randomly divided into four groups. The first group (the control group) and the remaining groups were dosed orally with estradiol (30 micrograms/kg) and corn oil (0.5 ml) for six weeks. Our study showed a significant increase in the progesterone, estrogen, and their receptors levels within the treated groups. Further, the histological examinations indicate an increase in ovarian follicles at different stages of development and numerous mature Graafian follicles. We noticed that there were more corpora lutea and the granulosa cell layer was thicker in the treated groups compared to the control group.Taken together, our data suggested that phytoestrogens have a mechanism of action that mimics the body's internal (endogenous) estrogens, especially in the growth and development of ovary tissue. Therefore, adopting a diet rich in plant estrogens for a long period can cause an increase in the level of internal estrogens and disrupt their function.

High-grade serous ovarian cancer (HGSOC) is a poor prognostic disease, especially in BRCA1/2 wild-type (BRCA-WT) patients with homologous recombination (HR) proficiency. These patients often show limited response to both platinum-based chemotherapy and PARP inhibitors. HR and non-homologous end joining (NHEJ) are the two major DNA double-strand break (DSB) repair pathways. HR is a precise repair mechanism for DSBs but is limited to S and G2 phases. In contrast, NHEJ functions more broadly throughout the cell cycle, including G1. We investigated whether inhibiting the G2/M checkpoint kinases PLK1 or WEE1 individually could disrupt mitotic control and expose therapeutic vulnerabilities in BRCA-WT/HR-proficient HGSOC cells. We evaluated cell cycle-targeted strategies to overcome HR-proficient chemoresistance using either volasertib (a selective PLK1 inhibitor) or adavosertib (a potent WEE1 inhibitor) in BRCA-WT/HR-proficient and BRCA-mutant/HR-deficient HGSOC models. Both agents induced DNA damage, impaired HR repair (reduced RAD51 foci), and triggered mitotic catastrophe-a form of cell death caused by defective mitosis and unresolved DNA damage-in BRCA-WT cells. Volasertib caused polyploidy and abnormal spindle formation, indicating mitotic slippage and cytokinesis failure, whereas adavosertib abrogated the G2/M checkpoint, forcing premature mitotic entry. In contrast, BRCA-mutant cells were resistant to either volasertib or adavosertib, consistent with sustained and functional NHEJ activity. This resistance was restored by the pharmacological or genetic inhibition of DNA-PKcs (DNA-dependent protein kinase, catalytic subunit), a prominent component of NHEJ. Functional and xenograft models confirmed selective vulnerability of BRCA-WT tumors to either PLK1 or WEE1 inhibition. Our work highlights a mechanistic framework linking cell cycle checkpoint inhibition to DNA repair pathway selectivity, providing a rationale for targeting mitotic regulators in HR-proficient ovarian cancer-a subgroup with high clinical unmet need.

Drug repurposing in gynaecological cancers: Proven drugs for new challenges.

To investigate the clinical features, treatment status and identify the prognostic factors of elderly patients with ovarian cancer. In this retrospective study, the clinical and survival data of 123 patients with ovarian cancer aged 65years or older who were treated in Shaanxi Cancer Hospital from June 2019 to June 2023 were collected, and the clinical and prognostic factors were extracted and analyzed. Among the 123 enrolled patients, 51.2% of the elderly patients with ovarian cancer received standard treatment, which includes surgery and chemotherapy with or without maintenance therapy, with no serious postoperative complications. Gene testing during treatment was just conducted in 30.9% of patients. The study found that surgery, standardized treatment, maintenance were linked to improved both PFS and OS, while age was only related to OS and > 71years old was ignificantly associated with worse OS. Multivariate analysis revealed that both surgery (HR = 0.155, 95%CI 0.05-0.484, P = 0.001) and maintenance treatment (HR = 0.163, 95%CI 0.059-0.447, P < 0.001) are identified as independent prognostic factors for PFS, whereas surgery alone (HR = 0.289, 95%CI 0.107-0.78, P = 0.014) emerged as an independent prognostic factor for OS. Our real-world study demonstrates that just a small number of elderly patients with ovarian cancer received standard treatment and gene testing during treatment;those patients who accepted surgery, standardized treatment and maintenance had a better PFS and OS; the prognosis is even worse for patients who are older than 71;surgery and maintenance treatment are identified as independent prognostic factors for PFS, whereas surgery alone emerged as an independent prognostic factor for OS.While these findings provide valuable insights, it is important to note that this was a single-center retrospective analysis, and further validation in larger, prospective cohorts is warranted.

To analyze the association between myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) and PARP inhibitors (PARPi), to explore predisposing factors, and to evaluate their effectiveness and safety in clinical practice. Observational, analytical and retrospective study including patients with ovarian cancer treated with olaparib or niraparib from 2014 to 2024. Primary endpoint was to identify the incidence and risk factors of secondary malignancy, considering treatment duration, BRCA mutation, lines of platinum-based chemotherapy and grade 3-4 adverse events (AEs). Overall survival (OS), progression-free survival (PFS), and AEs were recorded. Eighty patients were included. Six developed secondary MDS/AML, with an incidence of 11.6% (5/43) for olaparib and 2.7% (1/37) for niraparib. No significant correlation was found, except for hematological grade 3-4 AEs, associated with a higher risk of developing MDS/AML (OR: 32.3 p = 0.001). The median latency period was 8.8months (1.5-102.2). For olaparib, median PFS was 37.8months (95% CI 17.0-58.6); OS was not reached. For niraparib PFS was 10.0months (95% CI 7.4-12.5), OS 25.1months (95% CI 6.3-43.9). Grade 3-4 AEs occurred in 32.6% of olaparib and 35.2% of niraparib patients, mainly anemia and thrombocytopenia. PARPi are effective and generally with a manageable safety profile. However, secondary MDS and AML, though rare, remain serious adverse events with incompletely defined risk factors. The observed incidence, particularly with olaparib, is comparable to or higher than that reported in trials, though the sample size was limited. Close monitoring of hematologic AEs may be key to preventing these neoplasms.

DNA damaging agents boost the transcription of endothelin A receptor in high-grade serous ovarian cancer.

Platinum resistance remains a major obstacle to effective treatment and improved prognosis in ovarian cancer. Although 5-methylcytosine (m5C) RNA modification has been implicated in chemoresistance, its precise functional role in ovarian cancer remains unclear. In this study, we integrated RNA-Seq and single-cell transcriptomic data from cisplatin-resistant ovarian cancer cell lines and patient samples, identifying the m5C reader protein ALYREF as a key regulator of platinum resistance. Functional studies using ALYREF and NSUN2 knockdown, overexpression, and mutant constructs-combined with multi-omics analyses (RNA-Seq, m5C-BIS-Seq, and RIP-Seq)-revealed that ALYREF binds to m5C-modified LGR4 mRNA, enhancing its stability and promoting activation of the Wnt/β-catenin signaling pathway. Critically, this regulatory mechanism is dependent on NSUN2-mediated m5C modification of LGR4 mRNA. Together, our findings demonstrate that the NSUN2/ALYREF/LGR4 axis mediates platinum resistance through m5C-dependent stabilization of LGR4 and downstream Wnt signaling activation. Thus, targeting ALYREF may represent a promising strategy to overcome platinum resistance in ovarian cancer.

Despite therapeutic advances, ovarian cancer remains a major clinical challenge owing to its frequent metastasis and chemoresistance, which are often driven by cancer stem cells (CSCs) and proangiogenic signaling. Here we demonstrated that dihydroartemisinin (DHA), a derivative of the antimalarial drug artemisinin, inhibits CSC characteristics, tumor neovascularization and resistance to carboplatin via a microRNA-dependent mechanism in ovarian cancer. DHA substantially inhibited CSC properties, tumorigenicity and vascular endothelial growth factor A (VEGF-A)-mediated tumor neovascularization in ovarian cancer. Moreover, the combined treatment with DHA and carboplatin produced a synergistic effect that reduced tumor burden, chemoresistance and peritoneal dissemination in vivo. Mechanistically, DHA downregulated BMI-1 and VEGF-A/vascular endothelial growth factor receptor 2 (VEGFR2), which are critical factors in CSC maintenance and metastasis, via the upregulation of miR-200b. An analysis of ovarian tumor tissues collected from patients enrolled in our clinical cohort revealed that dual positivity for BMI-1 and VEGF-A was associated with poor progression-free survival. Overall, DHA targets the miR-200b-BMI-1/VEGF-A axis to suppress cancer stemness and metastatic potential, highlighting its therapeutic promise in overcoming the limitations of standard chemotherapy for ovarian cancer. The clinical trial number for this study is not applicable.

Evaluating patient perspectives about the acceptability of a novel prognostic gene expression signature for high grade serous ovarian cancer: The OTTA-SPOT study.

This meta-analysis sought to assess the efficacy and safety of poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi) as maintenance therapy for patients with newly diagnosed advanced ovarian cancer (OC). A comprehensive search was conducted across the PubMed, Medline, EMBASE, Cochrane Library, and Web of Science databases, up to 30 January 2025. Both pairwise meta-analysis and Bayesian network meta-analysis were employed. The primary end points were progression-free survival (PFS) and adverse events (AEs). A total of seven randomized controlled trials, encompassing 11 studies and 3220 patients, were included. PARPi maintenance therapy significantly improved PFS in patients with newly diagnosed OC. Subgroup analysis revealed PFS benefits across BRCA mutations, BRCA wild-type (BRCAwt), homologous recombination deficiency (HRD), and homologous recombination proficiency patients. However, no overall survival (OS) benefit was observed with PARPi maintenance therapy in either the overall or HRD populations. Notably, senaparib showed superior PFS efficacy compared to veliparib and niraparib. Additionally, PARPi treatment was associated with a significantly higher incidence of grade ≥3 AEs. PARPi showed efficacy in improving PFS as maintenance therapy for newly diagnosed advanced OC, although no OS advantage was observed. PROSPERO (CRD420251020275).

Long non-coding RNAs and VEGF in ovarian cancer: mechanisms and therapeutic potential.

BRCA1 (breast cancer 1, early onset) is originally identified as a tumor suppressor in hereditary breast and ovarian cancer. Recent studies have suggested that BRCA1 contributes to the cell fate decisions in mammary epithelium. Although BRCA1 has been shown to be expressed in the thymus, its physiologic role(s) in the thymus remain unclear. In this study, we found that BRCA1 was expressed in a subset of thymic medullary epithelial cells: epithelial cell adhesion molecule (EpCAM, CD326) positive, UEA-1 ligand positive, and Aire negative. To clarify its functional significance, we analyzed the differentiation of thymic epithelial cells in mice in which BRCA1 was specifically deleted in K14-expressing cells. Interestingly, conditional BRCA1-deficient mice displayed enhanced development of Hassall’s corpuscles. Notably, thymoproteasome catalytic subunit β5t (proteasome subunit beta 11), a marker of cortical thymic epithelial cells (cTECs), was frequently detected adjacent to Hassall’s corpuscles in BRCA1 knockout mice. In addition, medullary β5t+ cells appeared to differentiate into cTECs. In addition, BRCA1 deficiency led to increased generation of regulatory T cells. Thus, BRCA1 was also found to regulate epithelial differentiation in the thymus. Our observations in BRCA1-deficient mice may be relevant to understanding the immune system in human with BRCA1 germline mutations.