High-grade Serous Ovarian Cancer Research Articles

Potential Transcriptomic Biomarkers for Predicting Platinum-based Chemotherapy Resistance in Patients With High-grade Serous Ovarian Cancer.

Due to the absence of screening protocols, high-grade serous ovarian cancer (HGSOC) patients are frequently diagnosed at an advanced stage, which significantly reduces the survival rate. Moreover, relapse occurs in approximately 70% of HGSOC patients after primary treatment. Predicting resistance to primary chemotherapy remains a challenge. In the research setting, transcriptomic analyses have emerged as powerful tools for predicting which HGSOC patients are likely to benefit from primary treatment. The aim of this review was to investigate the literature demonstrating the potential of transcriptomic signatures as biomarkers for assessing the risk of resistance to platinum-based chemotherapy. We conducted a three-step search process on PubMed to systematically review English-language articles published between 2020 and 2024. From the 123 articles retrieved, we included 11 articles that investigated transcriptomic signatures by RNA sequencing in tissues from chemo-sensitive and -resistant HGSOC patients. We report the clinicopathological data of 727 patients in the experimental cohorts, transcriptomic signatures, and technical aspects. Finally, the review lists 15 publicly available datasets used in the included studies. Furthermore, we investigated the overlap of 167 differentially expressed genes retrieved across the various articles. We believe this review might offer valuable insights for further studies focusing on predicting platinum resistance and personalized treatments. In addition to discussing the latest findings and potential candidates, we highlight the challenges of validating biomarkers across studies and publicly available datasets. Transcriptomic signatures represent a potential tool for patient stratification, prognosis, and the potential adoption of long-term therapies, such as poly (ADP-ribose) polymerase inhibitors (PARPis).

3D organoid models for predicting drug response in platinum-sensitive, high-grade serous ovarian cancer

3D organoid models for predicting drug response in platinum-sensitive, high-grade serous ovarian cancer

Homologous recombination status in BRCA wild-type patients as a predictor of disease volume and surgical outcome in patients with high-grade serous ovarian cancer

Homologous recombination status in BRCA wild-type patients as a predictor of disease volume and surgical outcome in patients with high-grade serous ovarian cancer

Microenvironment cell populations are associated with clinical outcomes in high-grade serous ovarian cancer

Microenvironment cell populations are associated with clinical outcomes in high-grade serous ovarian cancer

Use of DNA methyltransferase inhibitor and poly(adenosine diphosphate ribose) polymerase inhibitor (PARPi) in the treatment of PARPi-resistant, high-grade serous ovarian cancer

Use of DNA methyltransferase inhibitor and poly(adenosine diphosphate ribose) polymerase inhibitor (PARPi) in the treatment of PARPi-resistant, high-grade serous ovarian cancer

Supervised machine learning with a novel set of 20 genes predicts the likelihood of early or late recurrence of high-grade serous ovarian cancer

Supervised machine learning with a novel set of 20 genes predicts the likelihood of early or late recurrence of high-grade serous ovarian cancer

Efficacy and safety of alpelisib plus olaparib versus chemotherapy among patients with platinum-resistant or refractory high-grade serous ovarian cancer without BRCA mutation: Primary analysis of the EPIK-O trial

Efficacy and safety of alpelisib plus olaparib versus chemotherapy among patients with platinum-resistant or refractory high-grade serous ovarian cancer without BRCA mutation: Primary analysis of the EPIK-O trial

Does cancer appearance reflect genetic status? The relationship between the gross appearance of high-grade serous ovarian cancer and BRCA mutation status

Does cancer appearance reflect genetic status? The relationship between the gross appearance of high-grade serous ovarian cancer and BRCA mutation status

Association of high-grade serous ovarian cancer sample clonality with clinical outcomes

Association of high-grade serous ovarian cancer sample clonality with clinical outcomes

Impact of the tumor microenvironment in splenic metastasis in high-grade serous ovarian cancer revealed by quantitative proteomics

Impact of the tumor microenvironment in splenic metastasis in high-grade serous ovarian cancer revealed by quantitative proteomics

Focal adhesion kinase inhibitors as maintenance therapy in a homologous recombination repair proficient high-grade serous ovarian cancer murine model

Focal adhesion kinase inhibitors as maintenance therapy in a homologous recombination repair proficient high-grade serous ovarian cancer murine model

P53 functional status is associated with survival among high-grade serous ovarian cancer patients with copy number signature one

p53 functional status is associated with survival among high-grade serous ovarian cancer patients with copy number signature one

A spatial proteomic study of platinum-refractory, high-grade serous ovarian cancer implicates dual AKT and WNT activity linked to an immunosuppressive tumor microenvironment

A spatial proteomic study of platinum-refractory, high-grade serous ovarian cancer implicates dual AKT and WNT activity linked to an immunosuppressive tumor microenvironment

Spatial transcriptomics characterizes high-grade serous ovarian cancer and its precursor lesions

Spatial transcriptomics characterizes high-grade serous ovarian cancer and its precursor lesions

RAS/RAF/MEK mutated high-grade serous ovarian cancer susceptible to Raf inhibition in vitro but not in vivo

RAS/RAF/MEK mutated high-grade serous ovarian cancer susceptible to Raf inhibition in vitro but not in vivo

A multiplex single-cell RNA-Seq pharmacotranscriptomics pipeline for drug discovery.

The gene-regulatory dynamics governing drug responses in cancer are yet to be fully understood. Here, we report a pipeline capable of producing high-throughput pharmacotranscriptomic profiling through live-cell barcoding using antibody-oligonucleotide conjugates. This pipeline combines drug screening with 96-plex single-cell RNA sequencing. We show the potential of this approach by exploring the heterogeneous transcriptional landscape of primary high-grade serous ovarian cancer (HGSOC) cells after treatment with 45 drugs, with 13 distinct classes of mechanisms of action. A subset of phosphatidylinositol 3-OH kinase (PI3K), protein kinase B (AKT) and mammalian target of rapamycin (mTOR) inhibitors induced the activation of receptor tyrosine kinases, such as the epithelial growth factor receptor (EGFR), and this was mediated by the upregulation of caveolin 1 (CAV1). This drug resistance feedback loop could be mitigated by the synergistic action of agents targeting PI3K-AKT-mTOR and EGFR for HGSOC with CAV1 and EGFR expression. Using this workflow could enable the personalized testing of patient-derived tumor samples at single-cell resolution.

Does maximal effort cytoreductive surgery after 6-cycles of chemotherapy play a role in the management of advanced ovarian cancer?

The current gold standard in the surgical management of advanced ovarian cancer recommended by ESGO and ASCO is complete resection of all visible disease. If this is not deemed possible in the upfront setting, then interval cytoreductive surgery should be undertaken after 3-4-cycles of neo-adjuvant chemotherapy. Occasionally, surgery in the interval setting may not be possible either due to factors associated with patient fitness, or due to persistence of disease in sites deemed unresectable on interval scanning. Limited published data assessing outcomes from surgery delayed to after 6-cycles of NACT (delayed cytoreductive surgery) suggests a potential benefit over no surgery and suggests that if interval cytoreductive surgery is not possible, then the clinician might consider delayed surgery on a case by case basis. We sought to review the outcomes of patients with Advanced Ovarian Cancer presenting to the Northern Gynaecological Oncology Centre who underwent delayed surgery. This study is a retrospective analysis looking at patients with epithelial ovarian cancer of FIGO stage IIIC and above, who were not deemed suitable to undergo either primary or interval cytoreductive surgery, referred to the Northern Gynaecological Oncology Centre Gateshead, UK, between January 2014 and December 2020. We compared survival outcomes in women receiving non-standard treatment for advanced ovarian cancer, comparing two groups of patients; those completing at least six cycles of platinum-based chemotherapy as part of their first-line treatment and not having surgery with those who received delayed cytoreductive surgery after completing of 6-cycles of primary chemotherapy. A total of 89 cases were included in the analysis and 78/89 patients had completed at least 6-cycles of primary chemotherapy in the first-line treatment setting without any attempt at surgical cytoreduction. 11/89 patients underwent DDS after completion of 6-cycles of primary chemotherapy. The majority of included cases 87/89 (98%) were high-grade serous ovarian cancer (HGSOC). Surgery and no-surgery groups were well matched in terms of stage comparison at presentation with an overall stage distribution of 62% FIGO stage IIIC, 10% stage IVA and 28% stage IVB. The surgery group were significantly younger than the no-surgery group with median age of 68 (interquartile range (IQR) 59-71years) and 77years (IQR 70-82years) (p < 0.01), respectively. The overall survival (OS) of the surgery and no-surgery groups was 25months and 23months, respectively (p = 0.38) with a median follow-up of 20months (IQR 11-29months). The 1year disease-specific mortality for both groups was 18%. Maximal effort cytoreductive surgery after 6-cycles is not associated with a survival benefit (even with complete cytoreduction) but may be considered in the context of symptomatic disease or for palliation of symptoms amenable to surgery.

Prognostic factors and overall survival among patients with ovarian cancer in the pre-PARP inhibitor era: the OCRWE-Finland study.

Despite recent treatment advances in ovarian cancer (OC), more real-world evidence studies investigating patient outcomes are needed. OCRWE-Finland was an observational cohort study investigating OC outcomes in Finland during the pre-PARP inhibitor era. Patients were diagnosed with OC between 2014 and 2019 in Finland. This analysis reports baseline characteristics of all patients, patients with high-grade serous OC (HGSOC), and overall survival (OS) for patients with HGSOC. Among 1,711 patients diagnosed with OC, 867 (51%) had HGSOC. The absence versus presence of visible residual disease post-debulking surgery was associated with improved OS for patients at stage III (n = 303; median: NR vs. 43 months; p = 0.005), but not stage IV (n = 118; median: 37 months vs. 40 months; p = 0.96). Bevacizumab treatment at any line at stages III/IV improved OS in the short-term only. Receiving versus not receiving bevacizumab at first-line for patients with visible residual disease post-debulking surgery was associated with improved OS at stage III (median: 48 months vs. 36 months; p = 0.003), but not stage IV (median: 42 months vs. 37 months; p = 0.26). Multivariate Cox regression analyses showed that stage IV at initial diagnosis and the presence of R2 classification post-debulking surgery resulted in poorer OS. In the pre-PARP inhibitor era, the absence versus presence of visible residual disease post-debulking surgery was associated with improved OS in stage III, but not stage IV HGSOC. First-line bevacizumab seemed to be beneficial in patients with stage III HGSOC and visible residual disease.

Developing a DNA Methylation Signature to Differentiate High-Grade Serous Ovarian Carcinomas from Benign Ovarian Tumors.

Epithelial ovarian cancer (EOC) represents a significant health challenge, with high-grade serous ovarian cancer (HGSOC) being the most common subtype. Early detection is hindered by nonspecific symptoms, leading to late-stage diagnoses and poor survival rates. Biomarkers are crucial for early diagnosis and personalized treatment OBJECTIVE: Our goal was to develop a robust statistical procedure to identify a set of differentially methylated probes (DMPs) that would allow differentiation between HGSOC and benign ovarian tumors. Using the Infinium EPIC Methylation array, we analyzed the methylation profiles of 48 ovarian samples diagnosed with HGSOC, borderline ovarian tumors, or benign ovarian disease. Through a multi-step statistical procedure combining univariate and multivariate logistic regression models, we aimed to identify CpG sites of interest. We discovered 21 DMPs and developed a predictive model validated in two independent cohorts. Our model, using a distance-to-centroid approach, accurately distinguished between benign and malignant disease. This model can potentially be used in other types of sample material. Moreover, the strategy of the model development and validation can also be used in other disease contexts for diagnostic purposes.

Robotic Rectosigmoid Resection with Totally Intracorporeal Colorectal Anastomosis (TICA) for Recurrent Ovarian Cancer: A Case Series and Description of the Technique.

Most patients with ovarian cancer relapse within 2 years. Prospective randomized trials, such as DESKTOP III and SOC-I, have shown the role of secondary cytoreduction in improving oncological outcomes in selected patients, when complete tumor resection is achieved. Recent retrospective series suggest that minimally invasive surgery is a feasible option in oligometastatic recurrences, such as rectal ones. Five patients with an isolated rectal recurrence infiltrating the bowel wall underwent a robotic rectosigmoid resection with totally intracorporeal colorectal anastomosis. The procedure began with retroperitoneal access to manage the vascular structures, followed by visceral resection with a minimally invasive approach. The standard steps of an en-bloc pelvic resection, including intracorporeal end-to-end anastomosis, were performed. The treatment data were evaluated. The mean age of the patients was 54 years, and their mean body mass index was 30. All patients had at least one previous abdominal surgery and 60% had high-grade serous ovarian cancer at their initial diagnosis. Their mean platinum-free interval was 17.4 months. Complete secondary cytoreduction was achieved in all cases, with histopathology confirming bowel infiltration. The mean procedure duration was 294 min, with an estimated blood loss of 180 mL. No intraoperative complications occurred. The mean hospital stay was 8 days. One patient had a grade 2 postoperative complication. The mean follow-up period was 14 months, with only one patient experiencing a recurrence at the level of the abdominal wall. Robotic rectosigmoid resection is a viable option for complete cytoreduction in isolated recurrent ovarian cancer.