A phase I dose-escalation study of Lobaplatin combined with paclitaxel in platinum-sensitive recurrent ovarian epithelial carcinoma: preliminary safety and tolerability supporting clinical trial dosing.

Ovulation-derived extracellular vesicles exhibit sustained oncogenic influence on the exposed fallopian tube fimbrial cells after drainage into peritoneal cavity.

Introduction: Ovarian cancer is one of the most common gynecological cancers in the United States. Common sites of distant metastasis from ovarian cancers and other cancers of Mullerian origin include the liver, pleura and lungs. However, metastasis to the brain remains exceptionally rare, ranging from 0.49 to 6.1%. Hence, the scarcity of such cases poses significant diagnostic and management challenges. Case Presentation: We present a case of an 80-year-old female who at the time of initial diagnosis presented with complaints of right leg pain, shortness of breath and cough. Imaging studies were remarkable for a pulmonary embolism, 2.5 cm mediastinal mass, pleural effusions, omental caking and an occlusive thrombus in the right greater saphenous vein. Malignancy was suspected in the setting of hypercoagulability. Biopsy of the omentum and pleural cytology revealed a high grade ovarian serous carcinoma. The patient received neoadjuvant chemotherapy followed by cytoreductive surgery and additional chemotherapy afterwards. She demonstrated good response to treatment with follow up PET without evidence of disease. Over the next four years, the patient was intermittently placed on chemotherapy when found to have elevated CA125 levels and PET scan showing small volume disease mostly in the pelvis. Six-years later, the patient presented to the oncology clinic with complaints of dizziness and imbalance for the past month. MRI brain showed a new left cerebellar mass with vasogenic edema and obstructive hydrocephalus. However, restaging CT chest, abdomen and pelvis showed minimal to no disease, with the only possible foci being a 1.2 cm paraaortic lymph node. The patient underwent left suboccipital craniotomy and cerebellar tumor resection with pathology showing metastatic carcinoma consistent with spread from a Mullerian primary. Conclusion: This case emphasizes the diagnostic complexity and evolving clinical course of Müllerian tumors. In a patient with a history of Mullerian tumor and new onset neurological symptoms, differential diagnosis should include metastasis to the brain, even with minimal to no active pelvic and systemic disease burden.

Uterine serous carcinoma (USC) is an aggressive p53-mutated endometrial carcinoma that exhibits gene mutations in homologous recombination (HR) pathways, similar to high-grade serous ovarian carcinoma (HGSOC). However, the therapeutic effect of PARP inhibitors on USC is limited. This study investigated cyclin-dependent kinase 12 (CDK12), a transcriptional regulator of HR genes, and evaluated the efficacy of a novel CDK12 inhibitor, CTX-439, combined with a PARP inhibitor, olaparib, in patient-derived xenograft (PDX) models of USC. We evaluated the homologous recombination deficiency (HRD) scores, genetic alterations, and HR-related gene abnormalities, including CDK12 in USC, other histopathological types of uterine endometrial carcinoma, and HGSOC using the Cancer Genome Atlas dataset. We also assessed CDK12 function and CTX-439 efficacy in USC utilizing USC cell lines and PDX models. USC exhibited a higher HRD score than other histological subtypes of uterine endometrial carcinoma but lower than HGSOC. CDK12 amplification occurred more frequently in USC than in HGSOC but was not associated with HRD scores. Tumors with CDK12 amplification demonstrated high CDK12 expression, which correlated with poor prognosis in USC. The CDK12 inhibitor CTX-439 suppressed HR-related gene expression, including BRCA1 and BRCA2, induced apoptosis and DNA damage, and inhibited tumor growth in USC PDX models with high CDK12 expression. Furthermore, CDK12 inhibition enhanced tumor sensitivity to the PARP inhibitor, olaparib in USC PDX models. This study indicates that CDK12 is a potential therapeutic target for enhancing the antitumor effects of PARP inhibitors in patients with USC.

Spontaneous Rupture of Ovarian Endometrioid Carcinoma in the First Trimester: A Case Report

Analysing cell death patterns to predict outcomes and treatment options in patients with high-grade serous ovarian carcinoma.

Introduction and Background: High-grade serous ovarian carcinoma (HGSOC) is notorious for its poor prognosis owing to its inherent biological aggressiveness and development of chemoresistance. The mechanistic target of rapamycin (mTOR) pathway is dysregulated in 55% of epithelial ovarian cancers, representing an appealing therapeutic target. To date, the clinical trials of mTOR inhibitors have shown modest response. In this study, we investigated the mTOR pathway in a clinical cohort of primary, chemo-naive, high-grade ovarian cancer samples, along with its regulatory post-transcriptional miRNA regulation. Methodology: We performed differential gene expression analysis on 100 HGSOC patients from TCGA and 80 healthy controls (i.e., normal ovarian tissue) from GTEx. The differentially expressed genes (DEGs) were overlaid onto the KEGG mTOR signalling pathway, followed by functional enrichment analysis. Next, we conducted differential miRNA expression analysis on the same cohort and identified regulatory miRNA-mTOR gene pairs involved in cancer pathogenesis. Finally, we constructed an interaction network and identified key hub genes and miRNAs with potential prognostic significance. Results: We identified 95 mTOR pathway genes that were significantly differentially expressed, involving upstream regulators, core components, and downstream effectors. Functional pathway analysis revealed a prominent shift toward mTORC1 activation, accompanied by paradoxical activation of autophagy. The let-7 miRNA family was identified as a key regulator of the mTOR pathway, potentially facilitating disease progression. RICTOR downregulation, a key component of the mTORC2 complex, appears to play a critical role in this histotype. In addition, FNIP1, a tumour suppressor gene implicated in mTOR dysregulation, was found to correlate with survival outcomes. Conclusions: We propose a model of dual activation of mTORC1 and autophagy in HGSOC as the metabolic rewiring enabling cancer progression under nutrient and cellular stress.

To investigate the effects of 20 kHz low-frequency ultrasound irradiation-mediated microbubbles (USMB) combined with chemotherapy paclitaxel and cisplatin (PC) on ovarian cancer cells. In the in vitro research, ovarian cancer cell lines were divided into four groups: control, USMB, PC, and USMB+PC. The cell membrane structure was observed using scanning electron microscopy (SEM). A TUNEL assay was used to investigate cell apoptosis. In the in vivo study, USMB+PC was used to treat the ascites in the nude mice. The ascites volumes were calculated by magnetic resonance imaging. In the ex vivo research, ascites samples of clinical ovarian cancer patients were collected and focused with USMB+PC and observed by liquid-based cytology. SEM revealed cell wall defects in the USMB and USMB+PC, with pores ranging from 5 to 15 μm in diameter. The USMB+PC had the highest apoptosis rate, with statistical differences compared to the other three groups (all p<0.05). After USMB+PC treatment, the volume of ascites in the nude mice decreased (t=3.6, p=0.0228). In the USMB+PC, tumour cells in the ascites showed obvious degeneration and necrosis. The mechanism is that US irradiation causes MBs to rupture, generating shock waves, damaging tumor cell walls, forming pores (sonoporation), leading to more drugs entering cancer cells. The clinical significance of this technology is that it can increase the dosage of locally targeted tumor cells, reduce systemic chemotherapy use/or the clinical dosage of chemotherapy drugs, and decrease the toxic side effects on normal tissue cells. The limitation is that there are relatively few cases of patients with ex vivo ascites. Future research direction is US irradiation on ex vivo ascites of ovarian cancer patients with different histological types. US cavitation and chemotherapy inhibit ovarian cancer cells.

Epithelial ovarian cancer is a heterogenous group, that includes histologic sub-types with distinct biologic behavior. Stage IC disease confers a higher risk of recurrence and death compared to stage IA. While adjuvant chemotherapy may improve outcomes of patients with high-grade serous ovarian carcinoma, its impact on the oncologic outcomes of other histologic sub-types that are more chemo-resistant, such as clear cell, mucinous, and low-grade serous ovarian carcinoma is not well-established. Retrospective studies have demonstrated that omission of adjuvant chemotherapy can be considered for patients with expansile mucinous, grade 1 endometrioid, and low-grade serous ovarian carcinoma and for those with stage IC1 clear cell ovarian carcinoma. However, in the absence of data from randomized clinical trials, shared decision-making, and careful counseling of patients should be considered. Future multicenter studies are required to further validate the safety of adjuvant chemotherapy omission in certain patient sub-groups with stage IC epithelial ovarian cancer.

High frequency of BRAF mutations and concomitant KRAS mutations in Taiwanese ovarian clear cell carcinoma.

AKR1C inhibitors medroxyprogesterone acetate and mefenamic acid exhibit antitumor activity alone and combined with carboplatin in platinum-resistant high-grade serous ovarian cancer models.

The development of translational ovarian cancer models to investigate and overcome treatment resistance, while accounting for the impact of the tumor microenvironment, is critical. Here, we present a protocol to establish a multicellular culture model that retains both genetic complexity and the microenvironment of patient tumors and is amenable to molecular and phenotypic analyses and high-throughput drug testing. We describe steps for culturing and characterizing stromal cells derived from cryopreserved and fresh samples and detail procedures for combining them with organoids.

Preparation of novel Mn-doped Ti-based organic frameworks for the sonodynamic therapy of serous ovarian carcinoma.

Uterine serous carcinoma (USC) is an aggressive histological subtype of endometrial cancer that frequently presents with early extrauterine spread, often without uterine symptoms. We report a diagnostically challenging case of a postmenopausal woman presenting with malignant ascites, peritoneal metastases and deep vein thrombosis, but no abnormal uterine bleeding. Preoperative imaging and biopsies were inconclusive, suggesting a possible leiomyoma or ovarian malignancy. Exploratory laparotomy revealed widespread peritoneal disease, and histopathology demonstrated serous carcinoma confined to an endometrial polyp with lymphovascular space invasion but no myometrial invasion. Immunohistochemistry showed p53 and p16 positivity, focal WT1 (Wilms tumor 1 protein) positivity, weak ER (estrogen receptor) expression and MMR (mismatch repair) proficiency, confirming primary USC (International Federation of Gynaecology and Obstetrics (FIGO) stage IVB). The patient was initiated on paclitaxel-carboplatin chemotherapy. This case highlights the diagnostic difficulties of USC, its potential to mimic ovarian carcinoma and the importance of integrating surgical, pathological and molecular evaluation for accurate diagnosis and management.

Successful closure of a recurrent enterocutaneous fistula using integrative traditional Chinese and Western medicine in ovarian cancer: A case report.

Patients with densely innervated tumors suffer with poor outcomes, thus identifying them could define a cohort that could benefit from aggressive treatments. Most cases and deaths from ovarian cancer are associated with high-grade serous ovarian carcinoma (HGSOC). We immunohistochemically analyzed the histological subtypes of ovarian cancer (high-grade serous, low-grade serous, clear cell, mucinous, and endometrioid) for nerves; only HGSOCs were densely innervated. We previously defined that tumor-released small extracellular vesicles (sEVs) recruit nerves to the tumor bed and thus tested whether the difference in nerve infiltration amongst ovarian cancers was associated with sEVs. Using an in vitro neurite outgrowth assay, we found that HGSOC sEVs harbored robust neurite outgrowth activity. Importantly, sEVs from fallopian tube cell lines (the primary cell of origin of HGSOC) predominantly lacked this activity. Implantation of a syngeneic mouse model of HGSOC into transgenic mice lacking tumor-infiltrating nerves slowed tumor growth, sensitized disease to carboplatin, and improved survival. Consistent with this, we show that recurrent, treatment-resistant disease in patients is significantly more innervated than its matched naïve (untreated) malignancy. Taken together, these data identify dense nerve infiltration of HGSOCs and show that innervation contributes to treatment resistance.

DNA Topoisomerase II Mutations in Cancer: Structural Impact and Drug Response in High-grade Serous Ovarian Carcinoma.

Clear cell ovarian carcinoma is a rare sub-type characterized by poor prognosis and intrinsic resistance to platinum-based chemotherapy. Unlike high-grade serous ovarian cancer, its distinct molecular profile suggests a potentially greater susceptibility to immunotherapy. However, available evidence remains limited and heterogeneous. This systematic review and meta-analysis evaluated the efficacy and safety of immune checkpoint inhibitors in this setting. PubMed, Embase, and Cochrane databases were searched through November 2025. Cohort studies and clinical trials enrolling patients with clear cell ovarian carcinoma alone or mixed ovarian and endometrial clear cell carcinoma were eligible. Immune checkpoint inhibitors administered as monotherapy or in combination with other systemic therapies were included. Outcomes were objective response rate, progression-free survival, overall survival, and treatment-related adverse events, including any-grade and grade ≥3 events. A random-effects model was used for pooled analyses with R software version 4.2.0. The study was registered in International Prospective Register of Systematic Reviews (CRD420251130819). Fifteen studies (423 patients), including 14 clinical trials and 1 cohort study, met eligibility criteria. The pooled objective response rate across all treatment cohorts was 24.5% (95% confidence interval [CI] 18.3 to 32.7, I2 = 61%, p < .01). Specifically, 14.6% for immune checkpoint inhibitor monotherapy (n = 122, 95% CI 8.8 to 24.2, I2 = 38%, p = .15) and 37.5% for dual blockage (n = 77, 95% CI 24.4 to 57.5, I2 = 42%, p = .16). Four studies (n = 130) provided re-constructable survival data, yielding a pooled median progression-free survival of 3.8 months and overall survival of 18.8 months. Severe treatment-related adverse events grade ≥3 occurred in 29.36% of patients (N = 288, 95% CI 20.30 to 42.47, I2 = 70%). Immune checkpoint inhibitors demonstrate modest clinical activity in clear cell gynecologic carcinomas, with higher response rates observed for dual agent. Treatment-related adverse events were frequent, underscoring the need for careful patient selection and toxicity monitoring. Substantial heterogeneity and limited survival data support the need for biomarker-driven prospective trials to better define which patients benefit the most.

Unexpected double-hit BRCA1/BRCA2 somatic mutations in a sporadic endometrioid ovarian carcinoma.

Accurately distinguishing between primary and gastrointestinal metastatic mucinous ovarian carcinoma (MOC) is crucial but remains highly challenging. We developed and validated the MOC Origin Prediction Model (MOCOPM), the deep learning model specifically designed to predict the origin of MOC from histopathology images. Cases of primary or gastrointestinal metastatic MOC were collected from three hospitals and divided into internal and external cohorts. Three neural networks were trained using the area under the receiver operating characteristic curve (AUROC) as the primary performance metric. After five-fold cross-validation on the internal cohort, the best-performing model was selected to construct MOCOPM, which was then externally validated. In total, 167 MOC patients were included. MOCOPM achieved an average AUROC of 0.91 internally and 0.96 externally. This model offers a promising tool to support clinical decision-making in MOC diagnosis.