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Cancers
Special Issues
Gynecologic Oncology: Clinical and Translational Research
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Gynecologic Oncology: Clinical and Translational Research

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 3810

Special Issue Editors

Dr. Gennaro Daniele

E-Mail Website
Guest Editor
Phase 1 Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Interests: phase I study; translational research; drug development; targeted therapy
Special Issues, Collections and Topics in MDPI journals
Dr. Pasquale Lombardi

E-Mail Website
Co-Guest Editor
Phase 1 Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Interests: phase I study; translational research; drug development; targeted therapy
Dr. Gaia Giannone

E-Mail Website
Co-Guest Editor
Department of Surgery and Cancer, Imperial College London, London, UK
Interests: translational research; ovarian cancer; gynecological cancers; PARP inhibitors; homologous recombination deficiency

Special Issue Information

Dear Colleagues,

Over the last few decades, the treatment of gynecological cancers has dramatically changed due to the introduction of immunotherapy in endometrial and cervical cancer and target therapies in ovarian cancer, with more and more improvements expected to come (e.g., antibody–drug conjugates, as well as new powerful combinations). This has led to modification of the treatment algorithm, as well as the use of new molecular tests and a more and more personalized approach. In this issue, we want to provide evidence on the management of these malignancies in the era of personalized medicine with a focus on real-world data on effectiveness and toxicity. Moreover, we will welcome translational studies regarding not only prognostic and predictive biomarkers, but also mechanisms of resistance to the current treatments and possible approaches to overcome them.

Dr. Gennaro Daniele
Dr. Pasquale Lombardi
Dr. Gaia Giannone
Guest Editors

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 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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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

  • gynecological cancer
  • ovarian cancer
  • translational research
  • effectiveness
  • toxicity
  • immunotherapy
  • PARP inhibitors

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Published Papers (5 papers)

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Research

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17 pages, 1515 KiB  
Article
Feasibility and Effects of Implementing Multimodal Prehabilitation Before Cytoreductive Surgery in Patients with Ovarian Cancer: The Gynofit Multicenter Study
by Stella van der Graaff, Tessa A. M. Backhuijs, Frank P. de Kort, Elize W. Lockhorst, Huberdina P. M. Smedts, Jennifer M. J. Schreinemakers, Gatske M. Nieuwenhuyzen-de Boer and Janneke S. Hoogstad-van Evert
Cancers 2025, 17(9), 1393; https://doi.org/10.3390/cancers17091393 - 22 Apr 2025
Viewed by 158
Abstract
Background: Cytoreductive surgery (CRS), in combination with chemotherapy, is the main treatment for advanced-stage ovarian cancer. In vulnerable patients, this extensive surgery has a high complication risk and may lead to clinical decline. There is emerging evidence that prehabilitation could be valuable [...] Read more.
Background: Cytoreductive surgery (CRS), in combination with chemotherapy, is the main treatment for advanced-stage ovarian cancer. In vulnerable patients, this extensive surgery has a high complication risk and may lead to clinical decline. There is emerging evidence that prehabilitation could be valuable in optimizing the patient’s condition prior to cytoreductive surgery, as is shown in colorectal surgery. However, there is limited evidence in gynecologic oncology. The objective of this study is to evaluate the feasibility and effects of implementing multimodal prehabilitation before cytoreductive surgery in patients with ovarian cancer. Methods: In two Dutch hospitals, 46 patients with ovarian cancer were included during the study period, of whom 32 participated in a multimodal prehabilitation program before CRS. The programs included at least physiotherapy, dietary advice and intoxication cessation. The timing, extent and content of the programs differed. Feasibility was assessed by eligibility and participation rates and adherence to the physiotherapy program. Effectiveness was measured by differences in functional capacity, postoperative outcomes and tolerance to adjuvant chemotherapy. Results: Eligibility rates in both hospitals were 83% and 89%, and participation rates were 68% and 72%. Adherence to the physiotherapy program was moderate and only satisfactory in 55% and 63% of the patients. All fitness endpoint measurements improved compared to the baseline. No significant differences in postoperative outcomes were found between prehabilitation and control patients. Prehabilitation patients appeared to have better tolerance to adjuvant chemotherapy, with fewer dose reductions (21% vs. 73%, p = 0.017) and dose deferrals (39% vs. 46%, not significant) compared to the control group. Conclusions: The implementation of multimodal prehabilitation before CRS is feasible and effective in patients with ovarian cancer with respectable eligibility and participation rates, along with improved functional capacity, even during neoadjuvant chemotherapy. Full article
(This article belongs to the Special Issue Gynecologic Oncology: Clinical and Translational Research)
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14 pages, 2220 KiB  
Article
Uterine Pgrmc2 Deficiency Attenuates Endometrial Hyperplasia and Cancer and Prolongs Lifespan in a Pten Loss-of-Function-Induced Cancer Model
by Nicole C. Kelp, Cindy A. Pru, Sandeep Paudel, John P. Lydon, J. Julie Kim, John J. Peluso and James K. Pru
Cancers 2025, 17(7), 1178; https://doi.org/10.3390/cancers17071178 - 31 Mar 2025
Viewed by 237
Abstract
The expression of members of the progesterone receptor membrane component (PGRMC) family, particularly PGRMC1, is elevated in diverse types of cancers, particularly those of the female reproductive system. While xenograft tumor studies using human transformed cell lines in immunocompromised mice have suggested that [...] Read more.
The expression of members of the progesterone receptor membrane component (PGRMC) family, particularly PGRMC1, is elevated in diverse types of cancers, particularly those of the female reproductive system. While xenograft tumor studies using human transformed cell lines in immunocompromised mice have suggested that PGRMC1 enhances tumor growth and chemoresistance, the exact role of members of the PGRMC family in cancer development in vivo remains unclear. In this study, we examined the effect of deleting Pgrmc2 on the development of endometrial hyperplasia and cancer using a murine phosphatase and tensin homologue (Pten) conditional loss-of-function model. We previously established that PGRMCs are cell survival factors that are required for normal estrogen-induced uterine epithelial cell proliferation and normal female fertility. The deletion of Pgrmc2 reduced the incidence and severity of endometrial hyperplasia and cancer in mice with conditional Pten-heterozygous uteri and increased lifespan in mice with conditional Pten-knockout uteri. Mechanistically, the deletion of Pgrmc2 decreased uterine glandular epithelial cell proliferation. Pten loss-of-function-induced endometrial hyperplasia and cancer elevated uterine inflammation, but this was not impacted by PGRMC2 deficiency. This study identifies PGRMC2 as a potential therapeutic target to be inhibited in the treatment of endometrial hyperplasia and cancer, particularly where PTEN activity is reduced due to gene mutation or loss. Full article
(This article belongs to the Special Issue Gynecologic Oncology: Clinical and Translational Research)
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10 pages, 464 KiB  
Article
Challenging the Binary Classification of Endometrioid Endometrial Adenocarcinoma: The Evaluation of Grade 2 as an Independent Entity Based on Prognostic Characteristics and Recurrence Patterns
by Andreas Zouridis, Ammara Kashif, Ahmed Darwish, Christina Pappa, Federico Ferrari, Sarah Louise Smyth, Negin Sadeghi, Alisha Sattar, Stephen Damato, Mostafa Abdalla, Sean Kehoe, Susan Addley and Hooman Soleymani Majd
Cancers 2025, 17(1), 127; https://doi.org/10.3390/cancers17010127 - 3 Jan 2025
Viewed by 813
Abstract
Background: Although grade is a well-recognised prognostic factor for endometrioid endometrial cancer (EEC), in more studies grade 1 (G1) and grade 2 (G2) EEC are combined and compared together with grade 3 (G3) tumours. The aim of our study is to separately investigate [...] Read more.
Background: Although grade is a well-recognised prognostic factor for endometrioid endometrial cancer (EEC), in more studies grade 1 (G1) and grade 2 (G2) EEC are combined and compared together with grade 3 (G3) tumours. The aim of our study is to separately investigate the outcomes, prognostic factors and recurrence patterns of G2 EEC and whether the differentiation between G1 and G2 EEC is clinically useful. Methods: we retrospectively reviewed 523 patients with EEC treated with primary surgery over a decade (March 2010–January 2020) at Oxford University Hospitals NHS Trust, focusing on those with G2 disease. Results: Patients with G2 EEC had worse 5-year cancer-specific survival (93.3% vs. 98.5%, p < 0.01) compared to patients with G1 EEC, but a favourable prognosis compared to G3 EEG, both in terms of disease-free survival (91.6 vs. 83.8%, p = 0.04) and cancer-specific survival (93.3% vs. 78.5%, p < 0.01). Both stage and grade are independent risk factors for cancer-specific mortality in EEC. Cervical stromal involvement, parametrial involvement and distant metastatic disease are all independent risk factors for cancer-related mortality in G2 ECC. Only 12.5% of recurrences of G2 EEC were diagnosed with examination in routine follow up in asymptomatic patients. Conclusions: our results suggest that the grading system should continue to differentiate G1 EEC and G2 EEC for better prognosis interpretation. Full article
(This article belongs to the Special Issue Gynecologic Oncology: Clinical and Translational Research)
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Review

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16 pages, 1514 KiB  
Review
Advanced Therapeutic Approaches for Metastatic Ovarian Cancer
by Soohyun Choe, Minyeong Jeon and Hyunho Yoon
Cancers 2025, 17(5), 788; https://doi.org/10.3390/cancers17050788 - 25 Feb 2025
Viewed by 739
Abstract
Ovarian cancer is the fifth leading cause of cancer-related death among women, which is one of the most common gynecological cancers worldwide. Although several cytoreductive surgeries and chemotherapies have been attempted to address ovarian cancer, the disease still shows poor prognosis and survival [...] Read more.
Ovarian cancer is the fifth leading cause of cancer-related death among women, which is one of the most common gynecological cancers worldwide. Although several cytoreductive surgeries and chemotherapies have been attempted to address ovarian cancer, the disease still shows poor prognosis and survival rates due to prevalent metastasis. Peritoneal metastasis is recognized as the primary route of metastatic progression in ovarian cancer. It causes severe symptoms in patients, but it is generally difficult to detect at an early stage. Current anti-cancer therapy is insufficient to completely treat metastatic ovarian cancer due to its high rates of recurrence and resistance. Therefore, developing strategies for treating metastatic ovarian cancer requires a deeper understanding of the tumor microenvironment (TME) and the identification of effective therapeutic targets through precision oncology. Given that various signaling pathways, including TGF-β, NF-κB, and PI3K/AKT/mTOR pathways, influence cancer progression, their activity and significance can vary depending on the cancer type. In ovarian cancer, these pathways are particularly important, as they not only drive tumor progression but also impact the TME, which contributes to the metastatic potential. The TME plays a critical role in driving metastatic features in ovarian cancer through altered immunologic interactions. Recent therapeutic advances have focused on targeting these distinct features to improve treatment outcomes. Deciphering the complex interaction between signaling pathways and immune populations contributing to metastatic ovarian cancer provides an opportunity to enhance anti-cancer efficacy. Hereby, this review highlights the mechanisms of signaling pathways in metastatic ovarian cancer and immunological interactions to understand improved immunotherapy against ovarian cancer. Full article
(This article belongs to the Special Issue Gynecologic Oncology: Clinical and Translational Research)
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12 pages, 877 KiB  
Review
Implications of Fumarate Hydratase Deficiency (FHD) and Cancer Risk: A Window into the Clinical and Oncological Implications of a Rare Disorder in Gynecology
by Marco D’Indinosante, Sara Lardino, Matteo Bruno, Guglielmo Stabile, Matteo Pavone, Gaia Giannone, Pasquale Lombardi, Gennaro Daniele, Francesco Fanfani, Francesca Ciccarone and Giovanni Scambia
Cancers 2025, 17(4), 573; https://doi.org/10.3390/cancers17040573 - 8 Feb 2025
Viewed by 1153
Abstract
Fumarate hydratase (FH) deficiency is a rare, yet impactful metabolic disorder caused by mutations in the FH gene, affecting the Krebs cycle, leading to the accumulation of fumarate and pseudohypoxic states. This metabolic shift promotes cell signaling alterations that can drive tumorigenesis, as [...] Read more.
Fumarate hydratase (FH) deficiency is a rare, yet impactful metabolic disorder caused by mutations in the FH gene, affecting the Krebs cycle, leading to the accumulation of fumarate and pseudohypoxic states. This metabolic shift promotes cell signaling alterations that can drive tumorigenesis, as heterozygous germline mutations in the FH gene, resulting in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. FH-deficient uterine leiomyomas show peculiar histological features that may lead to misdiagnosis STUMP (smooth muscle tumor of uncertain malignant potential) and uLMS (uterine leiomyosarcoma). Definitive diagnosis involves clinical evaluation, imaging, and histopathological examination, with immunohistochemistry for FH protein being a key diagnostic tool. Management of FH-deficient leiomyomas may involve conventional treatments like surgery and hormonal therapy but also requires careful monitoring and genetic counseling for associated malignancies. High-intensity focused ultrasound (HIFU) has emerged as a promising treatment option for fibroids, although long-term efficacy remains a concern also because of its inability to obtain tissue for a pathological diagnosis. Fumarate hydratase deficiency (FHD) represents a significant challenge in gynecologic oncology due to its association with an increased risk of hereditary leiomyomatosis and renal cell carcinoma. Nevertheless, to the best of our knowledge, there is a lack of studies demonstrating the potential role of FH deficiency in increased risk of leiomyosarcomatosus transformation. Early detection, genetic screening, and personalized treatment approaches are critical for improving patient outcomes. The aim of this review is to develop a narrative overview of the implications of FHD in gynecological diseases and its correlation with cancer risk. For the first time, this review offers an overview of the necessity for studies to address the possible correlation between FH deficiency and the risk of developing leiomyosarcoma, focusing on new perspectives that can be explored in the field of better FH deficiency knowledge and cancer risk. Full article
(This article belongs to the Special Issue Gynecologic Oncology: Clinical and Translational Research)
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