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Molecular Advances in Gynecologic Cancer
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Molecular Advances in Gynecologic Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 20 May 2025 | Viewed by 9071

Special Issue Editor

Dr. Alicja Forma

E-Mail Website
Guest Editor
Chair, Department of Anatomy, Medical University of Lublin, 20-090 Lublin, Poland
Interests: gynecologic cancer; homeostasis; liver; immune system
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Gynecologic cancers include those that affect the female reproductive organs, including five major types, namely ovarian, uterine, cervical, vaginal, and vulvar cancer, as well as the rare fallopian tube cancer. Research focused on the molecular characterization of particular types of cancers provides us with a better understanding of tumorigenesis as well as the pre-clinical management of various cancer types. Thus, molecular advancements in this matter provide us with the chance for advanced screening tests along with new diagnostic and prognostic markers. In this Special Issue, we would like to invite you to submit original research articles and comprehensive reviews about the recent molecular advancements in the field of gynecological oncology.

Dr. Alicja Forma
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.

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Keywords

  • ovarian cancer
  • uterine cancer
  • cervical cancer
  • vaginal cancer
  • vulvar cancer

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Published Papers (6 papers)

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Research

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16 pages, 9358 KiB  
Article
Targeting Signaling Excitability in Cervical and Pancreatic Cancer Cells Through Combined Inhibition of FAK and PI3K
by Chao-Cheng Chen, Suyang Wang, Jr-Ming Yang and Chuan-Hsiang Huang
Int. J. Mol. Sci. 2025, 26(7), 3040; https://doi.org/10.3390/ijms26073040 - 26 Mar 2025
Viewed by 354
Abstract
The Ras/PI3K/ERK signaling network is frequently mutated and overactivated in various human cancers. Focal adhesion kinase (FAK) is commonly overexpressed in several cancer types and has been implicated in treatment resistance mechanisms. A positive feedback loop between Ras, PI3K, the cytoskeleton, and FAK [...] Read more.
The Ras/PI3K/ERK signaling network is frequently mutated and overactivated in various human cancers. Focal adhesion kinase (FAK) is commonly overexpressed in several cancer types and has been implicated in treatment resistance mechanisms. A positive feedback loop between Ras, PI3K, the cytoskeleton, and FAK was previously shown to drive Ras signaling excitability. In this study, we investigated the effectiveness of targeting Ras signaling excitability by concurrently inhibiting FAK and PI3K in cervical and pancreatic cancer cells, which depend on activation Ras/PI3K signaling. We found that the combination of FAK and PI3K inhibitors synergistically suppressed the growth of cervical and pancreatic cancer cell lines through increased apoptosis and decreased mitosis. PI3K inhibitors alone caused only a transient suppression of downstream AKT activity and paradoxically increased FAK signaling in cancer cells. The addition of an FAK inhibitor effectively counteracted this PI3K-inhibitor-induced FAK activation. Furthermore, PI3K inhibitors were found to activate multiple receptor tyrosine kinases (RTKs), including insulin receptor, IGF-1R, EGFR, HER2, HER3, AXL, and EphA2. Taken together, our results suggest that FAK inhibition is necessary to counteract the compensatory RTK activation induced by PI3K inhibitors, thereby achieving more effective suppression of cancer cell growth. These findings highlight the therapeutic potential of combined FAK and PI3K inhibition in cancer treatment. Full article
(This article belongs to the Special Issue Molecular Advances in Gynecologic Cancer)
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18 pages, 484 KiB  
Article
MiR-205-5p and MiR-222-3p as Potential Biomarkers of Endometrial Cancer
by Anna Bogaczyk, Natalia Potocka, Sylwia Paszek, Marzena Skrzypa, Alina Zuchowska, Michał Kośny, Marta Kluz-Barłowska, Andrzej Wróbel, Jan Wróbel, Izabela Zawlik and Tomasz Kluz
Int. J. Mol. Sci. 2025, 26(6), 2615; https://doi.org/10.3390/ijms26062615 - 14 Mar 2025
Viewed by 422
Abstract
Endometrial cancer is the fourth most common cancer in women in Europe. Its carcinogenesis is a complex process and requires further research. In our study, we focus on finding new and easy-to-diagnose markers for detecting endometrial cancer. For this purpose, we compared the [...] Read more.
Endometrial cancer is the fourth most common cancer in women in Europe. Its carcinogenesis is a complex process and requires further research. In our study, we focus on finding new and easy-to-diagnose markers for detecting endometrial cancer. For this purpose, we compared the levels of miR-21-5p, miR-205-5p, and miR-222-3p in endometrial cancer tissues with the levels of these miRs in the serum of patients using the dPCR method. Our study is preliminary and consists of comparing the changes in miRNA expression in serum to the changes in miRNA in tissue of patients with endometrial cancer. The study included 18 patients with EC and 19 patients undergoing surgery for pelvic organ prolapse or uterine fibroids as a control group without neoplastic lesions. Endometrial tissue and serum were collected from all patients. The analyses showed an increased expression of miR-205-5p in endometrial cancer tissue and decreased expression of miR-222-3p in tissue and serum samples. These results suggest that miR-205-5p and miR-222-3p may be potential endometrial cancer biomarkers. Only miR-222-3p confirmed its decreased expression in serum, making it a potential and easily accessible marker in the diagnosis of endometrial cancer. This pilot study requires further investigation in a larger group of patients. Its advantages include the possibility of a comparison between miRNA expression in tissue and serum, as well as conducting the study using dPCR. Full article
(This article belongs to the Special Issue Molecular Advances in Gynecologic Cancer)
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12 pages, 2363 KiB  
Article
How Progesterone Receptor Expression Impacts Platinum Sensitivity in Ovarian Clear Cell Carcinoma: Insights from Clinical and Experimental Perspectives
by Chen-Hsuan Wu, Hung-Chun Fu, Yu-Che Ou, I-Chieh Chuang, Jui Lan, Ming-Yu Yang and Hao Lin
Int. J. Mol. Sci. 2024, 25(14), 7942; https://doi.org/10.3390/ijms25147942 - 20 Jul 2024
Viewed by 1264
Abstract
Ovarian clear cell carcinoma (OCCC) is often considered a relatively platinum-resistant malignancy. The aim of this study was to explore the influence of progesterone receptor (PR) expression levels on platinum sensitivity and survival outcomes in people with OCCC. A retrospective analysis was conducted [...] Read more.
Ovarian clear cell carcinoma (OCCC) is often considered a relatively platinum-resistant malignancy. The aim of this study was to explore the influence of progesterone receptor (PR) expression levels on platinum sensitivity and survival outcomes in people with OCCC. A retrospective analysis was conducted with 80 people with OCCC who underwent surgery followed by adjuvant chemotherapy. PR expression was assessed via immunohistochemical (IHC) staining and quantified using the H score. The platinum sensitivity and survival outcomes of patients with weak and strong PR expression were compared. Additionally, cisplatin viability and migration experiments were conducted with OCCC cell lines (ES-2 and TOV-21G) with varying PR isoform expressions. Among the 80 patients, 62 were classified as having platinum-sensitive disease, while 18 had platinum-resistant disease. The mean total PR H- score of platinum-sensitive tumors was significantly higher than that of platinum-resistant tumors (p = 0.002). Although no significant differences in progression-free and overall survival were observed between patients with high and low PR expression, those with high PR expression tended to have longer survival. While PR protein was only weakly detectable in ES-2 and TOV-21G cells, a transfection of the PR-A or PR-B gene resulted in a strong expression of PR-A or PR-B, which led to significantly reduced proliferation and migration in ES-2 and TOV-21G cells. Furthermore, overexpression of PR-A or PR-B enhanced cisplatin cytotoxicity in these cell lines. In conclusion, strong PR expression was associated with improved platinum sensitivity and survival outcomes, consistent with our experimental findings. The potential of PR as a tumor sensitizer to cisplatin in OCCC warrants further investigation. Full article
(This article belongs to the Special Issue Molecular Advances in Gynecologic Cancer)
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9 pages, 1331 KiB  
Article
Analysis of CDO1, PITX2, and CDH13 Gene Methylation in Early Endometrial Cancer for Prediction of Medical Treatment Outcomes
by Aleksey M. Krasnyi, Lyubov T. Gadzhieva, Diana N. Kokoeva, Mark G. Kosenko, Ekaterina L. Yarotskaya, Stanislav V. Pavlovich, Levon A. Ashrafyan and Gennady T. Sukhikh
Int. J. Mol. Sci. 2024, 25(9), 4892; https://doi.org/10.3390/ijms25094892 - 30 Apr 2024
Cited by 3 | Viewed by 1658
Abstract
An observational cohort study of patients diagnosed with endometrial cancer (EC) stage IA G1, or atypical endometrial hyperplasia (AEH), undergoing organ-preserving treatment, was conducted. Objective of the study: To determine CDO1, PITX2, and CDH13 gene methylation levels in early endometrial cancer [...] Read more.
An observational cohort study of patients diagnosed with endometrial cancer (EC) stage IA G1, or atypical endometrial hyperplasia (AEH), undergoing organ-preserving treatment, was conducted. Objective of the study: To determine CDO1, PITX2, and CDH13 gene methylation levels in early endometrial cancer and atypical hyperplasia specimens obtained before organ-preserving treatment in the patients with adequate response and with insufficient response to hormonal treatment. Materials and methods: A total of 41 endometrial specimens obtained during diagnostic uterine curettage in women with EC (n = 28) and AEH (n = 13), willing to preserve reproductive function, were studied; 18 specimens of uterine cancer IA stage G1 from peri- and early postmenopausal women (comparison group) were included in the study. The control group included 18 endometrial specimens from healthy women obtained by diagnostic curettage for missed abortion and/or intrauterine adhesions. Methylation levels were analyzed using the modified MS-HRM method. Results: All 13 women with AEH had a complete response (CR) to medical treatment. In the group undergoing organ-preserving treatment for uterine cancer IA stage G1 (n = 28), 14 patients had a complete response (EC CR group) and 14 did not (EC non-CR group). It was found that all groups had statistically significant differences in CDO1 gene methylation levels compared to the control group (p < 0.001) except for the EC CR group (p = 0.21). The p-value for the difference between EC CR and EC non-CR groups was <0.001. The differences in PITX2 gene methylation levels between the control and study groups were also significantly different (p < 0.001), except for the AEH group (p = 0.21). For the difference between EC CR and EC non-CR groups, the p-value was 0.43. For CDH13 gene methylation levels, statistically significant differences were found between the control and EC non-CR groups (p < 0.001), and the control and EC comparison groups (p = 0.005). When comparing the EC CR group with EC non-CR group, the p-value for this gene was <0.001. The simultaneous assessment of CDO1 and CDH13 genes methylation allowed for an accurate distinction between EC CR and EC non-CR groups (AUC = 0.96). Conclusion: The assessment of CDO1 and CDH13 gene methylation in endometrial specimens from patients with endometrial cancer (IA stage G1), scheduled for medical treatment, can predict the treatment outcome. Full article
(This article belongs to the Special Issue Molecular Advances in Gynecologic Cancer)
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Review

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42 pages, 545 KiB  
Review
Micro- and Macronutrients in Endometrial Cancer—From Metallomic Analysis to Improvements in Treatment Strategies
by Gabriela Hunek, Julita Zembala, Jacek Januszewski, Aleksandra Bełżek, Kinga Syty, Zoulikha Jabiry-Zieniewicz, Artur Ludwin, Jolanta Flieger and Jacek Baj
Int. J. Mol. Sci. 2024, 25(18), 9918; https://doi.org/10.3390/ijms25189918 - 14 Sep 2024
Cited by 1 | Viewed by 2065
Abstract
Endometrial cancer is reported to be one of the most prevalent cancers of the female reproductive organs worldwide, with increasing incidence and mortality rates over the past decade. Early diagnosis is critical for effective treatment. Recently, there has been a growing focus on [...] Read more.
Endometrial cancer is reported to be one of the most prevalent cancers of the female reproductive organs worldwide, with increasing incidence and mortality rates over the past decade. Early diagnosis is critical for effective treatment. Recently, there has been a growing focus on the role of nutrition and micronutrient and macronutrient status in patients with gynecologic cancers, including endometrial cancer. In the following paper, we have conducted an in-depth narrative literature review with the aim of evaluating the results of metallomic studies specifically concerning the micro- and macronutrient status of patients with endometrial cancer. The main objective of the paper was to analyze the results regarding the nutritional status of endometrial cancer patients and describe the role of chosen elements in the onset and progression of endometrial carcinogenesis. Further, we have focused on the evaluation of the usage of the described elements in the potential treatment of the abovementioned cancer, as well as the possible prevention of cancer considering proper supplementation of chosen elements in healthy individuals. Calcium supplementation has been proposed to reduce the risk of endometrial cancer, although some studies offer conflicting evidence. Deficiencies in phosphorus, selenium, and zinc have been inversely associated with endometrial cancer risk, suggesting they may play a protective role, whereas excessive levels of iron, copper, and cadmium have been positively correlated with increased risk. However, the molecular mechanisms by which these elements affect endometrial carcinogenesis are not fully understood, and current findings are often contradictory. Further research is needed to clarify these relationships and to evaluate the potential of nutritional interventions for the prevention and treatment of endometrial cancer. Full article
(This article belongs to the Special Issue Molecular Advances in Gynecologic Cancer)
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Graphical abstract

36 pages, 902 KiB  
Review
Micronutrient Status and Breast Cancer: A Narrative Review
by Alicja Forma, Arkadiusz Grunwald, Patryk Zembala, Jacek Januszewski, Adam Brachet, Roksana Zembala, Kamila Świątek and Jacek Baj
Int. J. Mol. Sci. 2024, 25(9), 4968; https://doi.org/10.3390/ijms25094968 - 2 May 2024
Cited by 6 | Viewed by 2500
Abstract
Breast cancer is one of the most common cancers worldwide, at the same time being one of the most prevalent causes of women’s death. Many factors such as alcohol, weight fluctuations, or hormonal replacement therapy can potentially contribute to breast cancer development and [...] Read more.
Breast cancer is one of the most common cancers worldwide, at the same time being one of the most prevalent causes of women’s death. Many factors such as alcohol, weight fluctuations, or hormonal replacement therapy can potentially contribute to breast cancer development and progression. Another important factor in breast cancer onset includes micronutrient status. In this narrative review, we analyzed 23 micronutrients and their possible influence on breast cancer onset and progression. Further, the aim of this study was to investigate the impact of micronutrient status on the prevention of breast cancer and its possible influence on various therapeutic pathways. We researched meta-analyses, systemic and narrative reviews, retrospective studies, as well as original studies on human and animal models. The results of these studies indicate a possible correlation between the different levels of micronutrients and a decreased risk of breast cancer as well as a better survival rate. However, further studies are necessary to establish adequate doses of supplementation of the chosen micronutrients and the exact mechanisms of micronutrient impact on breast cancer therapy. Full article
(This article belongs to the Special Issue Molecular Advances in Gynecologic Cancer)
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