Gynecologic Cancer Research Articles

To develop Deubiquitinase-Associated Signatures (DAS) to predict the prognosis of gynecological cancer patients. Using a Cox-Lasso regression model, we have developed deubiquitinase-associated signatures for Cervical, Ovarian, and Uterine cancers. Developed DAS were validated in TCGA and GEO datasets. Survival analysis was carried out to know the effect of factors Like menopausal stage and grade on DAS. The Survival prediction accuracy of DAS was analyzed using ROC curves. Immune infiltration scores of 22 immune subtypes were explored using theCIBERSORT package in risk groups classified by DAS. Further, to target the unfavorable deubiquitinases (DUBs), compounds were identified using CMap database. Three DAS were developed for Cervical, Ovarian, and Uterine cancer types. DAS was able to predict Survival and classify patients into two groups in TCGA and GEO datasets. DAS is an independent predictor of Survival irrespective of tumor grade and menopausal stage. DAS, along with the clinical features, improves the accuracy of predictions. CIBERSORT analysis has shown that immune cell infiltration is associated with risk groups divided by DAS. Using CMap, 52 compounds were identified to target unfavorable DUBs. DAS is a good predictor of survival, and targeting unfavorable DUBs may reduce tumor progression in gynecological cancers.

Factors that affect engagement with physical activity for patients who have received radiotherapy as part of their gynaecological cancer treatment - A rapid review.

Ovarian cancer (OV) is considered the most lethal gynecological cancer in women. Despite significant advancements in treatment and risk-stratification methods, these approaches remain far from ideal. This study aims to leverage large-scale public cohorts to identify differentially expressed prognostic genes between OV and normal ovarian tissue and evaluate their impact on patient survival. Utilizing data from extensive public cohorts and machine learning methods, we conducted a comprehensive screening to identify genes differentially expressed in ovarian cancer compared to normal ovarian tissue. We also developed a risk score for each patient based on these genes. Subsequent analyses explored the immunological profiles and genomic alterations associated with different risk scores. Our analysis revealed that a high risk score is positively correlated with poor survival in OV patients. The risk score is associated with key oncological pathways, immune-related processes, and genomic changes. Notably, patients with higher risk scores exhibited increased levels of immune cell infiltration and significant remodeling of the immune microenvironment. Furthermore, there is a strong correlation between the risk score and immune checkpoint molecules, suggesting potential benefits from immune checkpoint blockade strategies. The risk score also proved to be a stable and sensitive indicator for predicting sensitivity to various chemotherapeutic drugs. Through an integrative approach, our study deciphers the prognostic, immune, and therapeutic value of the risk score in OV. This analysis highlights the importance of the risk score in predicting survival, modulating immune response, and guiding chemotherapy sensitivity, thus supporting its utility in improving personalized treatment strategies for ovarian cancer patients.

Gynecological cancer remains one of the leading causes of mortality worldwide. Recent advances in genomic and molecular sequencing have significantly enhanced our understanding of the biological pathways that drive tumor progression and resistance to therapy. Targeted therapies, including monoclonal antibodies (mAbs), have revolutionized cancer treatment by selectively interfering with oncogenic proteins expressed on cancer cells. However, the long-term clinical benefit is often limited due to the emergence of drug resistance, frequently mediated by compensatory signaling pathways or immune escape mechanisms. To overcome these limitations, bispecific antibodies (bsAbs) represent an innovative class of therapeutic agents that have shown promising results across various medical fields. They have been developed to engage two distinct targets simultaneously, such as tumor antigens, immune effectors, or immunomodulatory checkpoints, thereby enhancing anti-tumor activity and reducing the risk of resistance. There are 17 bsAbs approved for clinical use in various countries, with numerous others currently in active development and over 600 bsAbs undergoing clinical trials worldwide. Among these, 11 have received FDA approval for the treatment of hematologic malignancies as well as solid tumors, including uveal melanoma, metastatic non-small cell lung cancer, small cell lung cancer, and biliary tract cancers. Although some studies have explored bsAbs in gynecological cancers, this area remains underdeveloped compared to other oncology fields. Most ongoing studies in this area are still in their early phases (phase I or phase II), and there is a need for optimization in terms of antibody design, efficacy, and safety profiles. Therefore, the purpose of this review is to present a comprehensive summary of the current research on bsAbs in gynecological cancers, with a focus on endometrial, cervical, and ovarian cancers. We will highlight ongoing clinical trials, discuss the mechanisms of action of these agents, and explore their potential benefits in enhancing treatment outcomes.

The current treatment of provoked vestibulodynia involving neuroproliferation is often complete vestibulectomy; however, less invasive treatments are biologically plausible, yet lack study. The International Society for the Study of Women's Sexual Health, the National Vulvodynia Association, the Gynecologic Cancers Research Foundation, and Tight Lipped, a grassroots nonprofit organization that supports people with chronic vulvovaginal and pelvic pain, collectively sponsored a conference, the Vulvodynia Therapeutic Research Summit, held in April 2024. The primary objective of the Vulvodynia Therapeutic Research Summit was to identify options for further research of the treatment of provoked vestibulodynia through expert consensus. After the conference, attendees scored the presented therapeutics in rank order, leading to a hierarchy of merit. Fifteen therapeutic options were presented and ranked in order of most promising to least promising for further study on treating the neuroinflammation of provoked vestibulodynia. The top identified therapeutics for further research were: 1) ketotifen fumarate (mast cell stabilizer with potential to prevent mast cell activation), 2) resiniferatoxin (transient receptor vanilloid 1 agonist causing chemo-inactivation of nerve terminals), 3) specialized pro-resolving mediators or strategies to boost their levels (eg, maresin 1 and 1-trifluoromethoxy-phenyl-3-(1-propionylpiperidin-4-yl) urea), 4) luteolin (flavonoid with potent anti-inflammatory, antioxidant, and neuroprotective properties), 5) alpha-lipoic acid (antioxidant with nerve-specific anti-inflammatory and mast cell stabilizing qualities), and 6) NGFR121W-SNAP IR700 trimer exposed to near-infared light (photoablation targeting nociceptors and sparing surrounding tissue). This executive summary describes the rationale for identifying specific pharmacologic agents and medical devices as targets for research directed toward treatment of the neuroinflammatory process found in the vestibular mucosa of provoked vestibulodynia.

Gynecological cancer poses a serious threat to women's health. Despite significant advances in immunotherapy and targeted therapeutic strategies for gynecological cancers, substantial challenges persist, including limited response rates, inevitable resistance, and adverse effects. In recent years, a milestone in gynecological cancer therapy has been the approval of antibody-drug conjugates (ADCs). In this review, we provide a comprehensive overview of the structural features, mechanisms of action, and molecular characteristics of ADCs that have been approved and are currently under development. Their clinical applications and associated challenges have also been highlighted. Finally, we discuss the prospects of ADCs in the treatment of gynecological cancers.

Ovarian cancer (OC) and endometrial cancer (EC) are highly heterogeneous gynecological malignancies with distinct molecular subtypes, therapeutic responses, and clinical outcomes. Traditional biopsy-based profiling often fails to capture the spatial and temporal complexity of these tumors. Radiogenomics, integrating imaging features with genomic and molecular data, has emerged as a promising approach to non-invasively analyze tumor heterogeneity. The purpose of this abstract is to critically examine and synthesize existing research on the application of radiogenomics in OC and EC, focusing on its ability to correlate imaging phenotypes with molecular biomarkers. This narrative review aims to demonstrate how radiogenomics can enhance tumor characterization, support biomarker prediction, and inform prognosis and therapeutic decision-making with non-invasive methods.This narrative review critically synthesizes current literature on radiogenomics applications in OC and EC. Studies using CT, MRI, and PET imaging were evaluated for their ability to correlate imaging phenotypes with molecular biomarkers, gene expression profiles, and clinical outcomes. The analysis emphasizes the role of radiogenomics in enhancing tumor characterization, predicting biomarker status, forecasting treatment response and prognosis.Radiogenomics has successfully identified associations between imaging features and key molecular alterations, such as BRCA mutations, homologous recombination deficiency (HRD), and immune-related biomarkers in OC, as well as POLE mutations, microsatellite instability (MSI), and tumor mutational burden (TMB) in EC. Predictive models incorporating radiomic features have demonstrated notable performance in estimating prognosis, treatment response, and recurrence risk across both cancer types.Radiogenomics has a strong potential to enhance personalized cancer care by analyzing tumor heterogeneity. However, clinical application requires methodological standardization, prospective validation, and integration into precision oncology workflows. · Radiogenomics enables non-invasive assessment of spatial and molecular heterogeneity in OC and EC.. · Integration of imaging and genomic data improves prediction of biomarkers, therapy response, and survival.. · Future clinical applications depend on methodological standardization, prospective validation, and integration into precision oncology workflows.. · Dolciami M, Celli V, Panico C et al. Unraveling Tumor Heterogeneity in Gynecological Cancer Using a Radiogenomics Approach Rofo 2025; DOI 10.1055/a-2698-8545.

Sentinel lymph node biopsy (SLNB) is a pivotal technique for evaluating regional lymphatic spread in breast, melanoma, and gynecologic malignancies. It minimizes surgical morbidity by avoiding complete lymphadenectomy in early-stage disease. The standard dual-tracer approach-combining a radiocolloid such as technetium-99m with a blue dye like patent blue or isosulfan blue-has high sensitivity but is not universally accessible. Radiocolloids require nuclear medicine facilities' licensing and pose logistical burdens, while patent blue may provoke allergic reactions, including anaphylaxis. These limitations are particularly pronounced in low- and middle-income countries (LMICs), where access and affordability are ongoing challenges. Methylene blue (MB), a low-cost, widely available dye, has gained traction as an alternative tracer, offering a safer and more feasible option for SLNB in resource-limited settings. This systematic review evaluates the diagnostic accuracy, detection reliability, and safety profile of methylene blue dye in SLNB across diverse oncologic sites, emphasizing comparing outcomes with traditional dual-tracer approaches. A systematic review of PubMed, Embase, Scopus, and Cochrane Library was conducted for studies published from 2000 to 2025. Inclusion criteria comprised clinical studies utilizing MB for SLNB in breast, melanoma, gynaecological, or other solid tumours, reporting outcomes such as detection rate, false-negative rate, or tracer-related complications. Data were extracted and synthesized descriptively. Where possible, pooled performance metrics were calculated. Twenty-five studies encompassing 5,240 patients were included. The pooled sentinel node detection rate using MB alone was 84.5% (72.0-96.2%), with a false-negative rate of 8.6%. When MB was combined with radiocolloid, detection rates improved to 96.1%, and false-negative rates dropped below 5%. Adverse effects were rare, with skin necrosis in fewer than 2% of cases and no serious allergic events reported. Most studies focused on breast cancer (18/25), while data on melanoma and gynecologic cancers were comparatively limited. Methylene blue is a viable alternative for SLNB, particularly in environments where dual-tracer methods are impractical. Though slightly less sensitive than dual-tracer techniques, MB offers substantial advantages in cost, safety, and accessibility. Further multicenter studies and long-term outcomes are needed to support its broader adoption in global oncology practice.

Therapeutic cancer vaccines represent a promising immunotherapy approach aimed at treating existing cancers by stimulating the patient’s immune system to target tumor cells. Unlike prophylactic vaccines, therapeutic vaccines are administered after cancer diagnosis and focus on inducing specific cytotoxic CD8 + T cell responses against tumor-associated antigens (TAAs) or tumor-specific neoantigens. These antigens are presented by antigen-presenting cells, such as dendritic cells, to activate an immune attack. However, the efficacy of therapeutic vaccines is often limited by immune tolerance, tumor heterogeneity, and an immunosuppressive tumor microenvironment, necessitating combination with other treatments like immune checkpoint inhibitors or chemotherapy. Multiple vaccine platforms are under investigation including peptide/protein-based, DNA/mRNA-based, dendritic cell vaccines, viral vector vaccines, and personalized neoantigen vaccines that leverage next-generation sequencing for precision targeting. Clinical trials target a range of cancers including melanoma, gynecologic, breast, pancreatic, liver, glioblastoma, and lung cancers, with results showing immune activation but modest clinical efficacy. Key challenges include immune evasion, variability in patient response, manufacturing complexities, high cost, and lack of predictive biomarkers. Technological advances in nanoparticle delivery, potent adjuvants, mRNA platforms, and combination immunotherapies are being explored to enhance vaccine performance. In low-resource settings, barriers such as limited access to advanced diagnostics and clinical trials necessitate tailored strategies to ensure equitable vaccine deployment. Overall, therapeutic cancer vaccines hold potential to become integrated into standard oncology protocols, especially for adjuvant therapy and recurrence prevention, with an emphasis on personalized and accessible immunotherapies to transform cancer management globally.

Ovarian cancer is the most lethal gynecologic cancer. This study explores differences in observed survival rates among ovarian cancer patients treated in certified versus non-certified hospitals in Germany. The study used data from German statutory health insurance (SHI) funds and clinical cancer registries (CCRs), including 20,794 insured and 4,493 registry patients diagnosed with a malignant ovarian neoplasm (ICD-10-GM code C56) from 2009 to 2017. Patients were categorized based on whether they received primary treatment at hospitals certified as ovarian cancer centers by the German Cancer Society (DKG) or at non-certified hospitals. Survival analyses were conducted using Kaplan-Meier and multivariable Cox regression methods. Adjustments were performed for age, year of diagnosis, International Union Against Cancer (UICC) stage, grade, lymphatic and venous invasion, year of index treatment, distant metastasis, Elixhauser comorbidities, and hospital criteria where available in the data source used. After adjustment for various confounders, treatment in certified centers was associated with a lower mortality risk, corresponding to a hazard ratio (HR) of 0.883 (95% CI 0.824-0.948; p = 0.001) in the SHI data. In the CCR data a non-significant HR of 0.964 was observed (95% CI 0.867-1.071; p = 0.490). Among patients in the CCR cohort diagnosed with UICC stage I-III disease, receiving treatment at certified centers was associated with improved survival outcomes (HR 0.825, 95% CI 0.708-0.961; p = 0.014). Treatment in DKG-certified centers is associated with better survival in ovarian cancer patients, especially in earlier stages. Certification status may be a relevant factor when choosing a treatment facility. ClinicalTrials.gov (identifier: NCT04334239). Retrospectively registered on 6 April 2020.

Endometrial cancer (EC) is the most common gynecologic cancer. Early detection is one of the most important predictors of survival. The cancer is curable if detected early but the five-year survival rate in advanced cases can be as low as 22%. Microsatellite instability (MSI) testing is used to screen populations for Lynch Syndrome (LS), the most common cause of inherited EC, and to classify EC into distinct groups with unique histological, prognostic, and molecular features. Accurate sample identification is crucial for successful MSI testing because instability is assessed by comparing amplification patterns in markers in the normal and tumor samples that must be taken from the same individual. Penta-C and Penta-D pentanucleotide markers are used widely for sample identification in not only MSI testing but also parentage verification, forensic science, and population genetics studies. The objective of this study was to test 324 pairs of tumor and matched normal DNAs from EC patients for instability in these markers using the Promega MSI Analysis SystemTM considered the “gold standard” in MSI testing. Both markers were unstable, and therefore not reliable for MSI testing, in 8.2% of the EC patients with MSI. Instability in both mono- and pentanucleotide markers suggest that the tumors with MSI likely suffer from a “generalized” form of instability also affecting other short tandem repeats. Results from many studies using these markers for various purposes may not be accurate if samples with MSI are involved.

Several European studies have shown health-related social inequalities in pelvic gynecological cancers, with a social gradient in incidence and mortality, partly explained by more advanced stages at diagnosis in low socioeconomic populations. Disparities in treatment and quality of care in these patients could be another cause of inequality in care. This study evaluates the impact of socioeconomic factors on quality of care for pelvic gynecological cancers (adnexal, uterine corpus, and cervix). This retrospective multicentric cohort study included women diagnosed with pelvic gynecological invasive cancer, between January 1 and December 31, 2022, in six university hospitals in North Paris. Two socioeconomic indicators, the FDep index and the Evaluation of Deprivation and Inequalities in Health Examination Centers (EPICES) score, were collected. The quality of care was assessed using a binary quality indicator based on selected European Society of Gynecological Oncology (ESGO) quality indicators for each cancer. We compared the "Non-adherence to Quality Indicator" (NAQI) group, where one or more of the ESGO quality indicators were not met, to the "Adherence to Quality Indicator" (AQI) group using univariate analysis. An analysis of the time to first treatment, according to FDep and EPICES groups, using a Kaplan-Meier, estimation was completed. A total of 189 patients were included: 50 with ovarian cancer, 76 with endometrial cancer, and 63 with cervical cancer. Ninety-nine patients (52.4%) belonged to the NAQI group and 90 patients (46.7%) to the AQI group. Patients were significantly in poorer general condition and presented more advanced Federation International of Gynecology Obstetrics (FIGO) stages in the NAQI than in the AQI group (ASA score 3-4: 20/84 [23.8%] vs. 5/76 (6.6%), P < 0.01 and FIGO III-IV stage: 55/99 [55.6%] vs. 35/90 [38.9%], P = 0.03). There was no significant difference for socioeconomic indicators between the NAQI and the AQI groups (FDep quintiles 3-4-5 = 41/99 (41.4%) vs. FDep quintiles 1-2 = 39/90 (43.3%), P = 0.91; EPICES score ≤ 30 = 31/63 (49.2%) vs. EPICES score > 30 = 21/51 (41.2%), P = 0.50). According to FDep and EPICES groups, we found no difference in the time to first treatment. We found no socioeconomic impact on hospital quality of care in pelvic gynecological cancers.

Radiotherapy remains crucial to the management of gynecologic cancers. This review highlights recent advances in radiation delivery, integration with systemic therapies, and the evolving role of radiotherapy across definitive, adjuvant, recurrent, and palliative settings. Trials in cervical cancer have established survival gains with novel systemic combinations, while adaptive and standardized radiation protocols continue to improve precision and outcomes. In endometrial cancer, molecular classification is informing adjuvant therapy selection and driving subtype-specific clinical trials. Expanding use of stereotactic body radiotherapy and proton therapy in ovarian and recurrent disease demonstrates feasibility and durable control. Efforts in reirradiation, palliative care, and survivorship underscore the need for safe dose escalation, symptom management, and long-term quality of life research. Persistent disparities and rising costs emphasize the importance of value-based and equitable care delivery. Emerging imaging and adaptive techniques are making radiation for gynecologic cancers more precise and individualized. Advances in brachytherapy, stereotactic approaches, and proton therapy are refining delivery, while integration with systemic and molecularly guided strategies is broadening therapeutic impact. Ongoing priorities include reducing disparities, improving survivorship, and translating technological progress into accessible, patient-centered care.

Predictors of Supportive Care in Young Adults Diagnosed With a Gynaecologic Malignancy.

Genomic distinctions in adolescent and young adult cancer: A comprehensive review.

Impact of social support on demoralization in patients with gynecological cancer: The chain mediating role of resourcefulness and resilience

Evaluating the efficacy of rTMS for the management of pain and psychological aspects in non-central nervous system cancer patients: a systematic review.

Breast and gynecological cancer risk in systemic lupus erythematosus: A meta-analysis of cohort studies.

Microplastic accumulation in endometrial cancer tissues and its metabolic impact.

Unraveling Tumor Associated Macrophage Biology in Gynecological Cancers for Targeted Therapy in the Single Cell Omics Era