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Gynecologic Oncology: Molecular Mechanisms and Therapies
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Gynecologic Oncology: Molecular Mechanisms and Therapies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 April 2026 | Viewed by 9231

Special Issue Editor

Dr. Angel Yordanov

E-Mail Website
Guest Editor
Department of Gynecological Oncology, Medical University Pleven, 5800 Pleven, Bulgaria
Interests: cervical cancer; endometrial cancer; treatment

Special Issue Information

Dear Colleagues,

This is our first Special Issue of the topic “Gynecologic Oncology: Molecular Mechanisms and Therapies”.

Gynecological cancers with major clinical significance and incidence that arise in the female reproductive organs include endometrial, cervical, ovarian, vaginal, and vulval cancers, along with gestational trophoblastic disease. Gynecological cancers implicate an important public health issue, with a spread among women of all ages. The disease is sometimes diagnosed at a late stage due to a lack of notice of specific symptoms, scarce screening, and sometimes misdiagnosis. Late diagnosis, together with limited treatment options for the advanced stages of cancer, play a pivotal role in the high mortality rate, and we are all aware of the necessity for further advancement in this sphere.

Recently, molecular mechanisms that influence the biological pathways involved in different cancers and regulate cancer-relevant processes have been demonstrated. The emergence of new genetic techniques has improved the understanding of the mechanisms essential for pathology. Such molecules and their interactions in the pathogenesis of gynecological malignancies have considerably ameliorated the management of the diagnosis and personalized treatment for different forms of cancer.

We are inviting submissions of original research articles, reviews, and communication on topics relevant to any aspect of gynecological cancer: molecular mechanisms in the pathogenesis of gynecological malignancies, diagnosis, and treatment for different forms of gynecological cancers.

Dr. Angel Yordanov
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 250 words) can be sent to the Editorial Office for assessment.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • cervical cancer
  • endometrial cancer
  • ovarian cancer
  • vulvar cancer
  • carcinogenesis
  • microinvairment
  • immunotherapy

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Published Papers (4 papers)

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Research

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26 pages, 6735 KB  
Article
The Emerging Role of FAM171A2 in Gynecological Malignancies: Bioinformatic Insights from UCEC and Ovarian Cancer
by Sibel Soylemez and Durmus Ayan
Int. J. Mol. Sci. 2025, 26(22), 11126; https://doi.org/10.3390/ijms262211126 - 18 Nov 2025
Viewed by 511
Abstract
The FAM171A2 gene encodes a transmembrane protein that is not well characterized but is implicated in signaling, vesicle trafficking, and interactions with the extracellular matrix. Its specific role in gynecologic malignancies has yet to be defined. To our knowledge, this is the first [...] Read more.
The FAM171A2 gene encodes a transmembrane protein that is not well characterized but is implicated in signaling, vesicle trafficking, and interactions with the extracellular matrix. Its specific role in gynecologic malignancies has yet to be defined. To our knowledge, this is the first systematic study to comprehensively assess FAM171A2 expression, clinical relevance, and molecular network interactions in gynecologic malignancies. We employed an integrative approach utilizing multi-platform transcriptomic and proteomic resources—GEPIA2, TNMplot, TIMER2, UALCAN, KM-plotter, Human Protein Atlas (HPA), Gene Expression Omnibus (GEO), STRING, TargetScan, and ENCORI—to comprehensively profile FAM171A2 expression, its clinicopathologic correlations, survival associations, predicted interaction networks, and post-transcriptional regulation in ovarian cancer (OV) and uterine corpus endometrial carcinoma (UCEC). Immunohistochemical analysis from the HPA indicated low or undetectable levels of the FAM171A2 protein in OV and UCEC. In contrast, RNA sequencing analyses demonstrated upregulated mRNA expression in OV and a modest, non-significant increase in UCEC compared to normal tissues. Pan-cancer screening using TNMplot and TIMER2 revealed elevated expression in gynecologic tumors relative to most other cancer types. In OV, UALCAN analysis identified associations with demographic and molecular characteristics, such as increased expression in TP53-mutant tumors, while trends related to stage and grade were minimal. Similarly, stratifications in UCEC suggested modulation by race, body mass index (BMI), and menopausal status rather than stage. Survival analyses using KM-plotter showed no significant association with overall survival in either type of cancer. TargetScan predicted 211 microRNAs potentially targeting FAM171A2, and ENCORI correlations supported tumor-type-specific post-transcriptional regulation: in OV, negative correlations were observed with miR-15b-5p, miR-16-5p, and miR-497-5p, along with long non-coding RNA (lncRNA) effects, including positive correlations with BACE1-AS and negative correlations with PVT1 and UCA1. In UCEC, significant negative correlations were found with LINC00582, LINC-ROR, MEG3, NEAT1, and SNHG12. STRING network analysis suggested two modules associated with FAM171A2: a neuronal/synaptic cluster, exemplified by NPTX1, and an immune/transcriptional cluster, exemplified by ZNF696. Validation using the GEO showed mixed results: two UCEC datasets were non-significant, whereas one OV cohort (GSE36368) exhibited higher tumor expression. FAM171A2 demonstrates context-dependent expressions that are modulated post-transcriptionally in gynecologic cancers. While it is not independently prognostic, it may serve as a molecular hub at the intersection of neuronal and immune pathways, warranting further mechanistic investigations and exploration as a panel-based biomarker. Full article
(This article belongs to the Special Issue Gynecologic Oncology: Molecular Mechanisms and Therapies)
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13 pages, 3687 KB  
Article
Apoptosis and G2/M Phase Cell Cycle Arrest Induced by Alkaloid Erythraline Isolated from Erythrina velutina in SiHa Cervical Cancer Cell
by Cleine Aglacy Nunes Miranda, Amaxsell Thiago Barros de Souza, Ana Katarina Menezes da Cruz Soares, Emanuelly Bernardes-Oliveira, Hugo Alexandre Oliveira Rocha, Euzébio Guimarães Barbosa, Thais Guaratini, Norma Lucena-Silva, Ricardo Ney Cobucci, Raquel Brandt Giordani and Janaina Cristiana de Oliveira Crispim
Int. J. Mol. Sci. 2025, 26(10), 4627; https://doi.org/10.3390/ijms26104627 - 12 May 2025
Cited by 1 | Viewed by 1370
Abstract
Cervical cancer remains a significant global health concern, causing more than 300,000 deaths annually. Erythrina velutina, a tree native to north-eastern Brazil, contains bioactive alkaloids with potential anticancer properties. This study aimed to characterize the alkaloid-enriched fraction of Erythrina velutina leaves and [...] Read more.
Cervical cancer remains a significant global health concern, causing more than 300,000 deaths annually. Erythrina velutina, a tree native to north-eastern Brazil, contains bioactive alkaloids with potential anticancer properties. This study aimed to characterize the alkaloid-enriched fraction of Erythrina velutina leaves and investigate the effects of the alkaloid erythraline on apoptosis and cell cycle in SiHa cervical cancer cells. Using Gas Chromatography–Mass Spectrometry (GC-MS), six alkaloids, including erythraline, were identified. Cytotoxicity was assessed through proliferation assays on SiHa cells and peripheral blood mononuclear cells (PBMCs). Apoptosis and cell cycle analyses were performed using flow cytometry, and in silico virtual screening identified potential protein targets of erythraline. Erythraline showed time- and concentration-dependent inhibitory effects on SiHa cell proliferation, with significant cytotoxicity observed at 50 µg/mL. Morphological changes, chromatin condensation, and increased apoptotic cell percentages confirmed the induction of caspase-independent apoptosis. Erythraline also induced G2/M cell cycle arrest, with 22% of cells in the G2/M phase compared with 7.25% in the untreated controls. In silico analysis identified polyamine oxidase, pyruvate kinase M2, and tankyrase as potential targets that contribute to the antitumor activity of erythraline. These findings suggest that erythraline is a promising candidate for anticancer therapy, warranting further investigation. Full article
(This article belongs to the Special Issue Gynecologic Oncology: Molecular Mechanisms and Therapies)
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17 pages, 2362 KB  
Article
Gemcitabine–Doxorubicin Combination Polymer-Drug Conjugate Prepared by SPAAC Click Chemistry: In Vitro Characterization
by Omotola D. Gbadegesin and Simeon K. Adesina
Int. J. Mol. Sci. 2025, 26(6), 2798; https://doi.org/10.3390/ijms26062798 - 20 Mar 2025
Cited by 1 | Viewed by 1558
Abstract
Combination chemotherapy is preferred for the treatment of ovarian cancer (OC). Systemic toxicity, however, frequently limits the effectiveness of treatment. Polymer–drug conjugates (PDCs) containing synergistic combinations of chemotherapeutic drugs can be used to enhance therapeutic efficacy. We earlier reported the use of a [...] Read more.
Combination chemotherapy is preferred for the treatment of ovarian cancer (OC). Systemic toxicity, however, frequently limits the effectiveness of treatment. Polymer–drug conjugates (PDCs) containing synergistic combinations of chemotherapeutic drugs can be used to enhance therapeutic efficacy. We earlier reported the use of a strain-promoted [3 + 2] azide–alkyne cycloaddition (SPAAC)-mediated polymerization method for the preparation of single-drug PDCs. In this report, the polymerization method was used to prepare gemcitabine–doxorubicin combination PDC. The PDC had a high molecular weight (Mw 1360 kDa) and high drug loading (36.6% weight gemcitabine; 7.0% weight doxorubicin). It demonstrated cathepsin B-catalyzed drug release at pH 5.0 and good hydrolytic stability at pH 7.4. The combination index analysis of free gemcitabine and free doxorubicin showed a concentration-dependent synergism (combination index < 1) in OVCAR-3 OC cells. Compared to individual gemcitabine PDC (the concentration that inhibited 50% growth (IC50) > 50 µg/mL) and doxorubicin PDC (IC50 = 1.79 µg/mL), the combination PDC (IC50 = 0.99 µg/mL) showed greater cytotoxicity against OVCAR-3 cells and was less cytotoxic than the equivalent free drug combination (IC50 = 0.11 µg/mL). The gemcitabine–doxorubicin combination PDC is promising for targeted combination chemotherapy of OC. Full article
(This article belongs to the Special Issue Gynecologic Oncology: Molecular Mechanisms and Therapies)
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Review

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18 pages, 7300 KB  
Review
Positivity Rate of PD-L1 Expression and Its Clinical Significance in Vulvar Cancer: A Systematic Review and Meta-Analysis
by Stefanos Flindris, Crysoula Margioula-Siarkou, Christos V. Chalitsios, Georgia Margioula-Siarkou, Emmanouela-Aliki Almperi, Aristarchos Almperis, Effrosyni Styliara, Konstantinos Flindris, Minas Paschopoulos, Iordanis Navrozoglou, Konstantinos K. Tsilidis, Konstantinos Dinas, Stamatios Petousis and Georgios Markozannes
Int. J. Mol. Sci. 2025, 26(10), 4594; https://doi.org/10.3390/ijms26104594 - 11 May 2025
Cited by 2 | Viewed by 5253
Abstract
The prevalence and prognostic value of programmed death ligand 1 (PD-L1) expression, as a potential biomarker in vulvar squamous cell carcinomas (VSCCs), remain underexplored. We searched the PubMed, Scopus, Embase, and Cochrane Library databases until July 2024 for articles examining PD-L1 expression in [...] Read more.
The prevalence and prognostic value of programmed death ligand 1 (PD-L1) expression, as a potential biomarker in vulvar squamous cell carcinomas (VSCCs), remain underexplored. We searched the PubMed, Scopus, Embase, and Cochrane Library databases until July 2024 for articles examining PD-L1 expression in VSCCs. Random-effects meta-analyses summarized PD-L1 expression overall and in subgroups by immunohistochemistry antibody type, positivity cutoff, tumor stage, and HPV positivity. Additionally, random-effects meta-analyses summarized the association between PD-L1 positivity and cancer prognosis. We included 26 studies comprising 1912 VSCC cases. The summary PD-L1 positivity rate in tumor cells was 59.9% (95% confidence interval [CI]: 47.7–71.4%; I2 = 96%, n = 26), influenced by the different cutoff thresholds utilized to define PD-L1 positivity. Compared to tumor cells, positivity rates were higher in intratumoral immune cells (75.6%; 95%CI: 52.9–92.5; I2 = 95.4%, n = 6) and peritumoral cells (78.9%; 95%CI: 54.4–95.5%; I2 = 91%, n = 3) but with overlapping 95%CIs. No heterogeneity was observed in the rates by tumor stage or HPV status. Positive PD-L1 expression was associated with worse overall (hazard ratio [HR] = 1.43; 95%CI: 1.06–1.93; I2 = 28.9%, n = 7) and progression-free survival (HR = 1.57; 95%CI: 1.07–2.3; I2 = 38.3%, n = 5). The PD-L1 expression rate in VSCC tumor cells varied across studies, was influenced by differences in immunohistochemical evaluation, and was identified as an unfavorable prognostic factor. Large, prospective, multicenter studies with standardized protocols are crucial to further elucidate the clinical significance of PD-L1 expression in VSCCs. Full article
(This article belongs to the Special Issue Gynecologic Oncology: Molecular Mechanisms and Therapies)
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