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Biomedicines
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Advanced Research in Gynecologic Oncology
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Advanced Research in Gynecologic Oncology

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 2900

Special Issue Editor

Dr. Abdelrahman AlAshqar

E-Mail Website
Guest Editor
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT 06510, USA
Interests: personalized treatment of ovarian cancer; molecular basis of endometrial cancer; disparties in cervical cancer; cardiovascular disease and gynecologic cancer

Special Issue Information

Dear Colleagues,

This Special Issue focuses on the latest advancements in the detection, treatment, and prevention of gynecologic cancers. Recent advances in gynecologic oncology have garnered much attention, and these include a broad range of emerging diagnostic methods, such as molecular biomarkers, liquid biopsy technologies, and advanced imaging techniques, with promising potential for early detection and the improvement of survival rates. In discussing therapeutic innovations, interested authors should emphasize cutting-edge treatments such as targeted therapies, immunotherapy (including immune checkpoint inhibitors and cancer vaccines), and novel chemotherapy agents, supported by the latest clinical trial data. Including insights into the molecular and genetic basis of gynecologic cancers, such as the role of BRCA mutations and other tumor-specific genetic alterations, is crucial for understanding the rationale behind personalized treatment approaches. Additionally, interested authors should consider the advancements made in minimally invasive surgical techniques, including robotic surgery, and their impact on patient outcomes. A key component should be the growing emphasis on improving the quality of life for survivors, addressing psychosocial and physical challenges post-treatment. Papers should also touch on the global impact of these cancers, addressing disparities in access to care and innovative strategies for overcoming barriers to treatment, especially in resource-limited settings. Overall, the submitted articles should present a multidisciplinary view of the interventions revolutionizing the field, integrating clinical, molecular, and social aspects of gynecologic oncology.

Dr. Abdelrahman AlAshqar
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • advancements
  • molecular techniques
  • endometrial cancer
  • personalized treatment
  • ovarian cancer
  • immunotherapy
  • gynecologic cancer outcomes

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Published Papers (5 papers)

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Research

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11 pages, 1133 KiB  
Article
Perma Curette and Hysteroscopy: An Observational Study About Endometrial Sampling
by Carmen Imma Aquino, Daniela Surico, Francesca Miglino, Arianna Ligori, Daniela Ferrante and Valentino Remorgida
Biomedicines 2025, 13(5), 1113; https://doi.org/10.3390/biomedicines13051113 - 4 May 2025
Viewed by 257
Abstract
The role of blind endometrial sampling, in the era of hysteroscopy-guided biopsy, can be only considered as a screening tool or a first-line approach if a hysteroscopy cannot be performed for whatever reason. Several devices are available, with Perma (a sharp-edged spatula sliding [...] Read more.
The role of blind endometrial sampling, in the era of hysteroscopy-guided biopsy, can be only considered as a screening tool or a first-line approach if a hysteroscopy cannot be performed for whatever reason. Several devices are available, with Perma (a sharp-edged spatula sliding inside a flexible cannula) being one of them. Objectives: The aims of this study were to compare the concordance of blind to visual endometrial sampling, and the influence of operators’ experience on the results. Materials and Methods: Women undergoing hysteroscopy were invited to undergo a Perma biopsy as well. If accepted, a Perma sampling was performed before the hysteroscopy and only if there was no cervical dilatation (as an office setting). The operator was randomly chosen between expert (two staff members) and non-expert (two residents) operators. All cases were collected at the AOU Maggiore della Carità, Novara, Italy. Categorical variables were presented in number and percentage (%) and continuous variables were presented as mean ± SD. The association between categorical variables was evaluated using Fisher’s exact test. Clinical outcomes were analyzed, and the results were first compared within the same patient and subsequent within the doctors’ group (inter- and intra-variation) in terms of Cohen’s Kappa. Results: 82 women performed both hysteroscopy and Perma. A sensitivity of 81.8% and specificity of 100% was found when Perma was compared to hysteroscopy (the gold standard). The comparison between valid vs. invalid samples in terms of sufficient evaluable tissue was not significant (p = 0.583). There are no statistical associations with body mass index, parity, or previous intrauterine surgery related to the outcomes of hysteroscopy and Perma. Cohen’s Kappa between non-experts was 0.43 (moderate), between experts was 0.30 (fair), with the highest concordance being between one non- and one expert (0.68 = substantial). Perma represents a pragmatic diagnostic tool, which could also be used in outpatient. Full article
(This article belongs to the Special Issue Advanced Research in Gynecologic Oncology)
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11 pages, 640 KiB  
Article
Neutrophil–Lymphocyte Ratio and KELIM Score as Prognostic Markers in High-Grade Serous Advanced Ovarian Cancer Patients Treated with Neoadjuvant Chemotherapy
by Vasilis Theodoulidis, Kalliopi Kissoudi, Kimon Chatzistamatiou, Panagiotis Tzitzis, Dimitris Zouzoulas, Iakovos Theodoulidis, Christos Anthoulakis, Theodoros Moysiadis, Maria Topalidou, Eleni Timotheadou, Grigoris Grimpizis and Dimitris Tsolakidis
Biomedicines 2025, 13(4), 975; https://doi.org/10.3390/biomedicines13040975 - 16 Apr 2025
Viewed by 332
Abstract
Background/Objectives: Advanced ovarian cancer (AOC) is frequently diagnosed at late stages, with a 5-year overall survival (OS) rate of approximately 25%. While primary debulking surgery followed by chemotherapy remains the standard treatment, neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is [...] Read more.
Background/Objectives: Advanced ovarian cancer (AOC) is frequently diagnosed at late stages, with a 5-year overall survival (OS) rate of approximately 25%. While primary debulking surgery followed by chemotherapy remains the standard treatment, neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is an alternative for patients with extensive disease. Achieving complete cytoreduction is a critical prognostic factor for OS and progression-free survival (PFS). This study evaluated the prognostic value of two biomarkers—the neutrophil–lymphocyte ratio (NLR) and the cancer antigen-125 (CA-125) ELIMination rate constant K (KELIM)—in predicting survival outcomes and recurrence rates in patients with AOC undergoing NACT. Methods: A retrospective, single-center analysis was conducted on 78 patients with high-grade serous AOC (stages III–IV) treated with platinum-based NACT followed by IDS between January 2013 and December 2023. NLR was calculated from prechemotherapy complete blood counts, with a threshold of ≥3 indicating elevated levels. KELIM, a marker of tumor chemosensitivity, was derived from CA-125 kinetics during the first 100 days of chemotherapy, with a cutoff of ≥1 denoting a favorable outcome. Clinical outcomes, including PFS and OS were analyzed using Kaplan–Meier survival curves, log-rank tests, and Cox regression models. Results: Results demonstrated that elevated NLR (≥3) and low KELIM (<1) were associated with poorer PFS and OS. KELIM score was identified as a strong prognostic marker for both PFS and OS, while NLR demonstrated weak association. Complete cytoreduction was achieved in 69.2% of patients, significantly correlating with improved survival outcomes. Postoperative complications, assessed using the Clavien–Dindo classification, were observed in a small subset of patients, with a total median hospital stay of 8 days. Conclusions: This study highlights the potential of NLR and KELIM as prognostic tools in AOC, aiding in patient selection for radical surgical interventions and predicting chemosensitivity. Future multicenter studies with larger cohorts are needed to validate these results and further explore the clinical utility of these biomarkers in optimizing treatment strategies for AOC. Full article
(This article belongs to the Special Issue Advanced Research in Gynecologic Oncology)
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19 pages, 4756 KiB  
Article
Integrative Bioinformatic Analysis of Cellular Senescence Genes in Ovarian Cancer: Molecular Subtyping, Prognostic Risk Stratification, and Chemoresistance Prediction
by Ailian Li and Dianbo Xu
Biomedicines 2025, 13(4), 877; https://doi.org/10.3390/biomedicines13040877 - 4 Apr 2025
Viewed by 493
Abstract
Background: Ovarian cancer (OC) is a heterogeneous malignancy associated with a poor prognosis, necessitating robust biomarkers for risk stratification and therapy optimization. Cellular senescence-related genes (CSGs) are emerging as pivotal regulators of tumorigenesis and immune modulation, yet their prognostic and therapeutic implications [...] Read more.
Background: Ovarian cancer (OC) is a heterogeneous malignancy associated with a poor prognosis, necessitating robust biomarkers for risk stratification and therapy optimization. Cellular senescence-related genes (CSGs) are emerging as pivotal regulators of tumorigenesis and immune modulation, yet their prognostic and therapeutic implications in OC remain underexplored. Methods: We integrated RNA-sequencing data from TCGA-OV (n = 376), GTEx (n = 88), and GSE26712 (n = 185) to identify differentially expressed CSGs (DE-CSGs). Consensus clustering, Cox regression, LASSO-penalized modeling, and immune infiltration analyses were employed to define molecular subtypes, construct a prognostic risk score, and characterize tumor microenvironment (TME) dynamics. Drug sensitivity was evaluated using the Genomics of Drug Sensitivity in Cancer (GDSC)-derived chemotherapeutic response profiles. Results: Among 265 DE-CSGs, 31 were prognostic in OC, with frequent copy number variations (CNVs) in genes such as STAT1, FOXO1, and CCND1. Consensus clustering revealed two subtypes (C1/C2): C2 exhibited immune-rich TME, elevated checkpoint expression (PD-L1, CTLA4), and poorer survival. A 19-gene risk model stratified patients into high-/low-risk groups, validated in GSE26712 (AUC: 0.586–0.713). High-risk patients showed lower tumor mutation burden (TMB), immune dysfunction, and resistance to Docetaxel/Olaparib. Six hub genes (HMGB3, MITF, CKAP2, ME1, CTSD, STAT1) were independently predictive of survival. Conclusions: This study establishes CSGs as critical determinants of OC prognosis and immune evasion. The molecular subtypes and risk model provide actionable insights for personalized therapy, while identified therapeutic vulnerabilities highlight opportunities to overcome chemoresistance through senescence-targeted strategies. Full article
(This article belongs to the Special Issue Advanced Research in Gynecologic Oncology)
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Review

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12 pages, 675 KiB  
Review
Mucinous Ovarian Carcinoma: Integrating Molecular Stratification into Surgical and Therapeutic Management
by Mauro Francesco Pio Maiorano, Brigida Anna Maiorano, Gennaro Cormio and Vera Loizzi
Biomedicines 2025, 13(5), 1198; https://doi.org/10.3390/biomedicines13051198 - 14 May 2025
Viewed by 290
Abstract
Background/Objectives: Mucinous ovarian carcinoma (MOC) is a rare and biologically distinct subtype of epithelial ovarian cancer, typically presenting at an early stage in younger women. Unlike high-grade serous carcinoma, MOC is characterized by unique molecular features—including frequent KRAS mutations and HER2 amplifications—and [...] Read more.
Background/Objectives: Mucinous ovarian carcinoma (MOC) is a rare and biologically distinct subtype of epithelial ovarian cancer, typically presenting at an early stage in younger women. Unlike high-grade serous carcinoma, MOC is characterized by unique molecular features—including frequent KRAS mutations and HER2 amplifications—and exhibits limited sensitivity to platinum-based chemotherapy. These differences highlight the need for individualized treatment strategies guided by molecular and histological profiling. This review aims to integrate current evidence on the clinical management of MOC with emerging insights into its molecular biology, with a focus on how these factors influence surgical decision-making, fertility preservation, and adjuvant therapy selection. Methods: We performed a comprehensive narrative review of the literature, synthesizing findings from retrospective cohorts, molecular studies, and clinical guidelines relevant to the surgical, reproductive, and therapeutic management of MOC. Results: Histologic subtype—expansile versus infiltrative—plays a critical role in guiding lymphadenectomy as lymph node metastases are rare (<1%) in expansile tumors but occur in up to 23% of infiltrative cases. Complete surgical staging remains essential for accurate prognostication, yet tailored approaches may reduce overtreatment in low-risk patients. Fertility-sparing surgery (FSS) appears safe in FIGO stage IA expansile MOC, with favorable reproductive outcomes, while higher-stage or infiltrative cases warrant caution. Given MOC’s chemoresistance, the role of adjuvant therapy in early-stage disease remains debated. Targeted strategies, including MEK inhibitors and HER2-directed therapies, are under investigation and may benefit selected molecular subgroups. Conclusions: MOC requires a nuanced, biomarker-informed approach. This review advocates for personalized, evidence-based management supported by multidisciplinary evaluation while underscoring the urgent need for prospective studies and biomarker-driven clinical trials. Full article
(This article belongs to the Special Issue Advanced Research in Gynecologic Oncology)
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27 pages, 1484 KiB  
Review
PARP Inhibitors in Ovarian Cancer: Resistance Mechanisms, Clinical Evidence, and Evolving Strategies
by Shant Apelian, Antons Martincuks, Michelle Whittum, Maya Yasukawa, Lindsey Nguy, Begum Mathyk, Vaagn Andikyan, Matthew L. Anderson, Thomas Rutherford, Mihaela Cristea, Daphne Stewart and Adrian Kohut
Biomedicines 2025, 13(5), 1126; https://doi.org/10.3390/biomedicines13051126 - 6 May 2025
Viewed by 388
Abstract
The introduction of poly (ADP-ribose) polymerase inhibitors (PARPi) into the management of ovarian cancer has transformed the treatment landscape for patients affected by this malignancy. However, as the use of PARPi expands into both frontline maintenance and recurrence settings, the emergence of drug [...] Read more.
The introduction of poly (ADP-ribose) polymerase inhibitors (PARPi) into the management of ovarian cancer has transformed the treatment landscape for patients affected by this malignancy. However, as the use of PARPi expands into both frontline maintenance and recurrence settings, the emergence of drug resistance has become a significant clinical challenge in the treatment of these patients. Although platinum-based chemotherapy (PBC) and PARPi act through different mechanisms—PBC causes DNA damage while PARPi blocks its repair—both depend on the integrity of DNA damage repair (DDR) pathways, leading to overlapping mechanisms of resistance. Here, we review the key resistance mechanisms shared by PARPi and PBC, and then we discuss their clinical implications in the management of patients with ovarian cancer. We also examine clinical rationale supporting the hypothesis that prior PARPi exposure may reduce the efficacy of subsequent PBC in patients experiencing a disease recurrence. Furthermore, we review preliminary clinical data assessing the potential role of PARPi retreatment in patients who have previously progressed on PARPis. Full article
(This article belongs to the Special Issue Advanced Research in Gynecologic Oncology)
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