Treatment Of Ovarian Cancer Research Articles

Past and present: a bibliometric study on the treatment of recurrent ovarian cancer.

Ovarian cancer (OC) is a gynecological malignancy with a high mortality rate worldwide. The unfavorable prognosis of OC is mainly attributed to the recurrent propensity. Recently, mortality from OC has exhibited a downward trend. These favorable patterns are likely to be driven by advancements in novel therapeutic regimens. However, there is a lack of visualize analysis of the application of these new drugs on women with recurrent OC (ROC). Therefore, we aimed to provide a bibliometric analysis of the evolving paradigms in the ROC treatment. Documents on ROC treatment were systematically collected from the MEDLINE database and Web of Science Core Collection (WOSCC). The retrieved documents were exported in the plain text file format, and files were named and saved to the paths specified by the Java application. Microsoft Excel (version 2010), Citespace (6.2.R4) and VOSviewer (1.6.19) were used for data analysis, and included the following: 1) annual publication trend; 2) contributions of countries, institutions and authors; 3) co-citation of journals and references; and 4) co-occurrence of keywords. A total of 914 documents published in the MEDLINE and 9,980 ones in WOSCC were retrieved. There has been an upward trend in the productivity of publications on ROC treatment on by years. The United States was the leading contributor in this field, and the University of Texas System stood out as the most productive institution. Giovanni Scambia and Maurie Markman were the research leaders in the field of ROC treatment. The journal Gynecologic Oncology had the highest citation frequency. The reference entitled with "Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer" got highest centrality of 0.14 in the co-citation network. Keyword analysis revealed that the focus of current ROC treatment was on platinum-based anticancer drugs, paclitaxel, angiogenesis inhibitors (AIs), immune checkpoint inhibitors (ICIs) and poly (ADP-ribose) polymerase inhibitors (PARPis). Scholars from a multitude of countries have been instrumental in the advancement of ROC treatment. The research hotspots and trend in the field of predominantly originated from leading international journals and specialized periodicals focused on gynecologic oncology. Maintenance therapy using AIs or (and) PARPis has emerged as a significant complement to platinum-based chemotherapy for patients with ROC.

Targeted Nanocarrier-Based Drug Delivery Strategies for Improving the Therapeutic Efficacy of PARP Inhibitors against Ovarian Cancer.

The current focus of ovarian cancer (OC) research is the improvement of treatment options through maximising drug effectiveness. OC remains the fifth leading cause of cancer-induced mortality in women worldwide. In recent years, nanotechnology has revolutionised drug delivery systems. Nanoparticles may be utilised as carriers in gene therapy or to overcome the problem of drug resistance in tumours by limiting the number of free drugs in circulation and thereby minimising undesired adverse effects. Cell surface receptors, such as human epidermal growth factor 2 (HER2), folic acid (FA) receptors, CD44 (also referred to as homing cell adhesion molecule, HCAM), and vascular endothelial growth factor (VEGF) are highly expressed in ovarian cancer cells. Generation of active targeting nanoparticles involves modification with ligands that recognise cell surface receptors and thereby promote internalisation by cancer cells. Several poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are currently used for the treatment of high-grade serous ovarian carcinomas (HGSOC) or platinum-sensitive relapsed OC. However, PARP resistance and poor drug bioavailability are common challenges, highlighting the urgent need to develop novel, effective strategies for ovarian cancer treatment. This review evaluates the utility of nanoparticles in ovarian cancer therapy, with a specific focus on targeted approaches and the use of PARPi nanocarriers to optimise treatment outcomes.

Anti-cancer effects of nitazoxanide in epithelial ovarian cancer in-vitro and in-vivo

Epithelial ovarian cancer is one of the most lethal gynecologic malignancies and poses a considerable threat to women's health. Although the progression-free survival of patients has been prolonged with the application of anti-angiogenesis drugs and Poly (ADP-ribose) polymerases (PARP) inhibitors, overall survival has not substantially improved. Thus, new therapeutic strategies are essential for the treatment of ovarian cancer. Nitazoxanide (NTZ), an FDA-approved anti-parasitic drug, has garnered attention for its potential anti-cancer activity. However, the anti-tumor effects and possible underlying mechanisms of NTZ on ovarian cancer remain unclear. In this study, we investigated the anti-tumor effects and the mechanism of NTZ on ovarian cancer in vitro and in vivo. We found that NTZ inhibited the proliferation of A2780 and SKOV3 epithelial ovarian cancer cells in a time- and concentration-dependent manner; Furthermore, NTZ suppressed the metastasis and invasion of A2780 and SKOV3 cells in vitro, correlating with the inhibition of epithelial-mesenchymal transition; Additionally, NTZ suppressed the Hippo/YAP/TAZ signaling pathway both in vitro and in vivo and demonstrated a good binding activity with core genes of Hippo pathway, including Hippo, YAP, TAZ, LATS1, and LATS2. Oral administration of NTZ inhibited tumor growth in xenograft ovarian cancer mice models without causing considerable damage to major organs. Overall, these data suggest that NTZ has therapeutic potential for treating epithelial ovarian cancer.

Homologous recombination deficiency status predicts response to immunotherapy-based treatment in non-small cell lung cancer patients.

Homologous recombination deficiency (HRD) is a biomarker that predicts response to ovarian cancer treatment with poly (ADP-ribose) polymerase (PARP) inhibitors or breast cancer treatment with first-line platinum-based chemotherapy. However, there are few studies on the prognosis of lung cancer patients treated with immune checkpoint inhibitor (ICI) therapy using HRD as a biomarker. We studied the relationship between HRD status and the effectiveness of first-line ICI-based therapy in EGFR/ALK wild-type metastatic non-small cell lung cancer patients (NSCLC) patients. This study included 22 treatment naïve NSCLC patients. The HRD score ranged from -26.37 to 92.34, with an average of 24.57. Based on analysis of the progression-free survival (PFS) data from the included NSCLC patients, threshold traversal was carried out. HRD (+) was defined as an HRD score of 31 or higher. Kaplan-Meier PFS survival analysis showed prolonged median PFS (mPFS) in NSCLC patients with HRD (+) versus HRD (-) (N/A vs. 7.0 ms, log-rank p = 0.029; HR 0.20, 95% CI: 0.04-0.96, likelihood-ratio p = 0.03). In patients with PD-L1 TPS ≥50% and HRD score ≥31 (co-status high), the mPFS was temporarily not reached during the follow-up period. In patients with PD-L1 TPS <1% and HRD score <31, the mPFS was 3 ms. Cox regression analysis showed that the hazard ratio of the co-status was 0.14 (95% CI: 0.04-0.54), which was a good prognostic factor, and the prognostic effect of co-status was better than that of HRD score alone. The HRD status can be identified as an independent significance in NSCLC patients treated with first-line ICI-based therapy.

Single-cell RNA sequencing reveals that MYBL2 in malignant epithelial cells is involved in the development and progression of ovarian cancer.

Ovarian carcinoma (OC) is a prevalent gynecological malignancy associated with high recurrence rates and mortality, often diagnosed at advanced stages. Despite advances in immunotherapy, immune exhaustion remains a significant challenge in achieving optimal tumor control. However, the exploration of intratumoral heterogeneity of malignant epithelial cells and the ovarian cancer tumor microenvironment is still limited, hindering our comprehensive understanding of the disease. Utilizing single-cell RNA sequencing (scRNA-seq), we comprehensively investigated the cellular composition across six ovarian cancer patients with omental metastasis. Our focus centered on analysis of the malignant epithelial cells. Employing CytoTRACE and slingshot pseudotime analyses, we identified critical subpopulations and explored associated transcription factors (TFs) influencing ovarian cancer progression. Furthermore, by integrating clinical factors from a large cohort of bulk RNA sequencing data, we have established a novel prognostic model to investigate the impact of the tumor immune microenvironment on ovarian cancer patients. Furthermore, we have investigated the condition of immunological exhaustion. Our study identified a distinct and highly proliferative subgroup of malignant epithelial cells, known as C2 TOP2A+ TCs. This subgroup primarily consisted of patients who hadn't received neoadjuvant chemotherapy. Ovarian cancer patients with elevated TOP2A expression exhibited heightened sensitivity to neoadjuvant chemotherapy (NACT). Moreover, the transcription factor MYBL2 in this subgroup played a critical role in ovarian cancer development. Additionally, we developed an independent prognostic indicator, the TOP2A TCs Risk Score (TTRS), which revealed a correlation between the High TTRS Group and unfavorable outcomes. Furthermore, immune infiltration and drug sensitivity analyses demonstrated increased responsiveness to Paclitaxel, Cisplatin, and Gemcitabine in the Low TTRS Group. This research deepens our understanding of malignant epithelial cells in ovarian cancer and enhances our knowledge of the ovarian cancer immune microenvironment and immune exhaustion. We have revealed the heightened susceptibility of the C2 TOP2A+ TCs subgroup to neoadjuvant chemotherapy and emphasized the role of MYBL2 within the C2 subgroup in promoting the occurrence and progression of ovarian cancer. These insights provide valuable guidance for the management of ovarian cancer treatment.

Interference with ANXA8 inhibits the malignant progression of ovarian cancer by suppressing the activation of the Wnt/β-catenin signaling pathway via UCHL5.

Ovarian cancer (OC), which threatens women's lives, is a common tumor of the female reproductive system. Annexin A8 (ANXA8) is highly expressed in OC. However, the mechanism of ANXA8 in OC remains unclear. This study investigated the potential mechanisms of ANXA8 in OC. The expression of ANXA8 in OC cells was determined by qRT-PCR and western blotting. ANXA8 interference plasmid was constructed. Moreover, CCK-8, EDU staining, TUNEL staining, western blotting, wound healing, and transwell assays were used to detect cell proliferation, apoptosis, migration, and invasion, respectively. Next, the relationship between ANXA8 and ubiquitin C-terminal hydrolase L5 (UCHL5) was verified through Co-IP. Finally, western blotting was used to detect the expression of Wnt/β-catenin signaling-related proteins. Additionally, we further interfered ANXA8 in nude mice with OC, and detected the expression of ANXA8, UCHL5 and the signaling pathway-related proteins by immunohistochemistry and western blotting. Our results suggested that ANXA8 expression was significantly increased in OC cells. ANXA8 interference significantly attenuated the proliferative, invasive, and migratory capabilities and promoted the apoptotic ability of OC cells. Moreover, the expression of UCHL5 in OC was significantly increased. ANXA8 bound to UCHL5 in OC cells. Knockdown of ANXA8 attenuated OC cell malignant progression by downregulating the expression of UCHL5. Furthermore, ANXA8 affected the expression of Wnt/β-catenin signaling pathway-related proteins in OC cells via UCHL5. Collectively, ANXA8 interference suppressed the activation of Wnt/β-catenin signaling pathway via UCHL5 to inhibit cell proliferation, invasion, migration and induce cell apoptosis in OC, thus presenting a potential therapeutic strategy for OC treatment.

Effects of PARP Inhibitors on Subsequent Platinum-Based Chemotherapy in Patients with Recurrent Ovarian Cancer.

The clinical outcomes in patients with ovarian cancer have been significantly improved by Poly(adenosine diphosphate-ribose) polymerase inhibitors (PARP-is). However, the best therapeutic strategy for recurrence during PARP-i maintenance therapy remains unknown. Herein, we elucidated the efficacy of platinum-based chemotherapy after PARP-i treatment in recurrent ovarian cancer. Eligible patients had experienced relapses during PARP-i maintenance therapy lasting at least 6 months and had received subsequent platinum-based chemotherapy at our institution between January 2019 and March 2024. Progression-free survival (PFS), overall survival (OS), and risk factors for PFS were evaluated. Sixty-six patients were assessed for eligibility and eighteen were enrolled. The median follow-up period was 14.5 months. The PFS and OS of all patients were 6.5 and 17.6 months, respectively. The evaluation of the risk factors for PFS revealed that age, pathological type, duration of PARP-i maintenance therapy, prior lines of chemotherapy, and PARP-i dose reduction were not significant prognostic markers. However, bevacizumab use in subsequent therapies significantly extended the PFS. The median PFS was 3.1 months in the chemotherapy-alone group and 8.9 months in the chemotherapy with bevacizumab group (log-rank p = 0.022). Platinum-based chemotherapy with bevacizumab in subsequent therapies would provide substantial benefits in the PFS of patients with recurrent ovarian cancer.

Interpretable machine learning model based on clinical factors for predicting muscle radiodensity loss after treatment in ovarian cancer.

Muscle radiodensity loss after surgery and adjuvant chemotherapy is associated with poor outcomes in ovarian cancer. Assessing muscle radiodensity is a real-world clinical challenge owing to the requirement for computed tomography (CT) with consistent protocols and labor-intensive processes. This study aimed to use interpretable machine learning (ML) to predict muscle radiodensity loss. This study included 723 patients with ovarian cancer who underwent primary debulking surgery and platinum-based chemotherapy between 2010 and 2019 at two tertiary centers (579 in cohort 1 and 144 in cohort 2). Muscle radiodensity was assessed from pre- and post-treatment CT acquired with consistent protocols, and a decrease in radiodensity ≥ 5% was defined as loss. Six ML models were trained, and their performances were evaluated using the area under the curve (AUC) and F1-score. The SHapley Additive exPlanations (SHAP) method was applied to interpret the ML models. The CatBoost model achieved the highest AUC of 0.871 (95% confidence interval, 0.870-0.874) and F1-score of 0.688 (95% confidence interval, 0.685-0.691) among the models in the training set and outperformed in the external validation set, with an AUC of 0.839 and F1-score of 0.673. Albumin change, ascites, and residual disease were the most important features associated with a higher likelihood of muscle radiodensity loss. The SHAP force plot provided an individualized interpretation of model predictions. An interpretable ML model can assist clinicians in identifying ovarian cancer patients at risk of muscle radiodensity loss after treatment and understanding the contributors of muscle radiodensity loss.

Cold atmospheric plasma-activated medium for potential ovarian cancer therapy.

Cold atmospheric plasma (CAP) has emerged as an innovative tool with broad medical applications, including ovarian cancer (OC) treatment. By bringing CAP in close proximity to liquids such as water or cell culture media, solutions containing reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated, called plasma-activated media (PAM). In this systematic review, we conduct an in-depth analysis of studies focusing on PAM interactions with biological substrates. We elucidate the diverse mechanisms involved in the activation of different media and the complex network of chemical reactions underlying the generation and consumption of the prominent reactive species. Furthermore, we highlight the promises of PAM in advancing biomedical applications, such as its stability for extended periods under appropriate storage conditions. We also examine the application of PAM as an anti-cancer and anti-metastatic treatment for OC, with a particular emphasis on its ability to induce apoptosis via distinct signaling pathways, inhibit cell growth, suppress cell motility, and enhance the therapeutic effects of chemotherapy. Finally, the future outlook of PAM therapy in biomedical applications is speculated, with emphasis on the safety issues relevant to clinical translation.

Bufalin: A promising therapeutic drug against the cisplatin-resistance of ovarian cancer by targeting the USP36/c-Myc axis

Cisplatin (DPP) resistance is a severe obstacle to ovarian cancer (OC) treatment. Our research aims to uncover the therapeutic effect and the underlying mechanism of Bufalin against DDP resistance. The cell viability, proliferation capacity, γH2AX expression, and apoptosis ratio were quantified via CCK8 assay, colony formation assay, immunofluorescence, and flow cytometry analysis respectively. Xenografting experiment was performed to detect the tumor growth. Molecular docking was applied to mimic the combination of Bufalin and USP36 protein, and Western blotting was conducted to measure the Bax, Bcl-2, γH2AX, USP36, and c-Myc expression. The c-Myc ubiquitination and half-life were detected via ubiquitination assay and cycloheximide chasing assay. Bufalin treatment notably suppressed the cell viability and colony numbers, and increased the apoptosis ratio and γH2AX level in the DDP treatment group. Bufalin therapy also notably inhibited tumor growth, Bax, Bcl-2, and γH2AX expression in vivo. Moreover, the Bufalin application remarkedly reduced the c-Myc expression and half-life and increased the c-Myc ubiquitination via interaction and subsequent down-regulation of USP36. Knockdown of USP36 reversed the antiproliferative effect and proapoptotic capacity of Bufalin therapy in the DDP treatment group. In conclusion, Bufalin can overcome the DDP resistance in vitro and in vivo via the USP36/c-Myc axis, which innovatively suggests the therapeutic potential of Bufalin against DDP resistance ovarian cancer.

Secondary Cytoreductive Surgery in Relapsed Platinum-Sensitive Epithelial Ovarian Cancer: A Systematic Review of Randomized Controlled Trials.

Secondary cytoreductive surgery is a treatment option for relapsed platinum-sensitive epithelial ovarian cancer, but no clear indications are defined for the procedure. This systematic review aims to establish clear indications and compare outcomes versus standard-of-care chemotherapy. We conducted an electronic literature search across three databases and identified 2033 articles, including three phase 3 randomized controlled trials (RCT). The review adhered to PRISMA 2020 guidelines and was registered in PROSPERO (no. CRD42022379817). Despite varying patient selection methods, surgery plus chemotherapy demonstrated significantly prolonged progression-free survival compared to chemotherapy alone. However, overall survival outcomes were inconsistent: while GOG-0213 did not show extended overall survival, recent studies with stricter defined criteria for surgery (SOC-1 and DESKTOP-III) reported improved overall survival with the addition of surgery. Morbidity and mortality rates were low, with no difference in quality of life between the surgery and no-surgery groups. In conclusion, cytoreductive surgery presents a promising option for recurrent epithelial ovarian cancer treatment. Nonetheless, well-defined selection criteria appear crucial for achieving increased overall survival compared to conventional treatment.

Circular RNA circ_ARHGEF28 inhibits MST1/2 dimerization to suppress Hippo pathway to induce cisplatin resistance in ovarian cancer

BackgroundCisplatin is integral to ovarian cancer treatment, yet resistance to this drug often results in adverse patient outcomes. The association of circular RNA (circRNA) with cisplatin resistance in ovarian cancer has been observed, but the mechanisms governing this relationship require further elucidation.MethodsHigh-throughput sequencing was utilized to profile circRNA expression in cisplatin-resistant ovarian cancer cells. Gain-and-loss-of-function experiments assessed the impact on cisplatin sensitivity, both in vitro and in vivo. Fluorescence in situ hybridization was conducted to determine the cellular distribution of circRNAs, and RNA pulldown and immunoprecipitation experiments were performed to identify associated binding proteins.ResultsThe study revealed that circ_ARHGEF28 is overexpressed in certain cisplatin-resistant ovarian cancer tissues and cell lines, and is associated with reduced progression-free survival in patients. It was observed that circ_ARHGEF28 contributes to cisplatin resistance in ovarian cancer models, both in vitro and in vivo. Importantly, circ_ARHGEF28 was found to interact directly with MST1/2, inhibiting the SARAH coiled-coil binding domains and consequently deactivating the Hippo pathway.ConclusionThis investigation identifies circ_ARHGEF28 as a novel circRNA that contributes to cisplatin resistance in ovarian cancer by suppressing the Hippo pathway. Therapeutic strategies targeting circ_ARHGEF28 may offer a potential avenue to mitigate cisplatin resistance in ovarian cancer treatment.

A peptide-salinomycin conjugate with a bystander effect reduces the stemness characteristics of ovarian cancer cells and enhances drug sensitivity

Salinomycin (Sal) has attracted considerable attention in the field of tumor treatment, especially for its inhibitory effect on cancer stem cells (CSCs) and drug-resistant tumor cells. However, its solubility and targeting specificity pose significant challenges to its pharmaceutical development. Sal-A6, a novel peptide-drug conjugate (PDC), was formed by linking the peptide A6 targeting the CSC marker CD44 with Sal using a specific linker. This conjugation markedly enhances the physicochemical properties of Sal and compared to Sal, Sal-A6 demonstrated a significantly increased activity against ovarian cancer. Furthermore, Sal-A6, employing a disulfide bond as a linker, exhibited bystander killing effect. Moreover, it induces substantial cytotoxic effect on both cancer stem cells and drug-resistant cells in addition to enhance chemosensitivity of resistant ovarian cancer cells. In summary, the results indicated that Sal-A6, a novel PDC derived from Sal, has potential therapeutic applications in the treatment of ovarian cancer and drug-resistant patients. Additionally, this discovery offers insights for developing PDC-type drugs using Sal as a foundation.

Diagnosis, treatment and burden in advanced ovarian cancer: a UK real-world survey of healthcare professionals and patients.

Aim: Little is known regarding uptake of epithelial ovarian cancer (EOC) treatments or patient burden in UK real-world practice.Methods: Cross-sectional surveys of patients with advanced EOC and healthcare professionals (HCPs).Results: 101 HCPs and 142 patients participated. Time from initial primary care consultation to diagnosis was ∼7weeks. 83% patients were offered hereditary genetic testing, with 89% uptake. 53% HCPs reported surgery was performed ≤1month in non-neoadjuvant setting. Surgery delay negatively impacted patient quality of life(61%), mental health (89%), and surgical outcomes (63%). 56% patients received active first-line maintenance treatment; patients on active surveillance had greater emotional/psychological distress.Conclusion: Treatment delays and low uptake of active first-line treatment should be addressed. Emotional support must be readily accessible throughout treatment.

First-line PARP inhibitor maintenance treatment in ovarian carcinoma for older adult women: a review of the current literature.

Ovarian cancer (OC) is the leading cause of death in women with gynecological cancers. Its diagnosis is more likely in advanced ages, with the older population being the most seen in consultations. Poly(ADP-ribose) inhibitors (PARPi) have changed OC clinical practice and evolution, showing great benefit. However, there is a lack of evidence of PARPi in elderly population that can impact the therapeutic decision and the safety/efficacy. It is necessary to avoid age as limiting factor in PARPis prescription. We conducted a review of the most relevant randomized phase III trials of maintenance PARPi after first-line treatment of advanced OC. We observed the lack of a single criterion for considering older patients, varying among trials. There is a benefit of PARPis in different populations. However, PARPi effect on quality of life is not reported, something of great relevance considering their vulnerability. Measures are needed to benefit older patients to better adapt PARPi treatment.

Pixantrone as a novel MCM2 inhibitor for ovarian cancer treatment

BackgroundMini-chromosome maintenance protein 2 (MCM2) is a potential target for the development of cancer therapeutics. However, small molecule inhibitors targeting MCM2 need further investigation. MethodsMolecular dynamics simulation was performed to identify active pockets in the MCM2 protein structure (6EYC). The active pocket was used as a docking model to discover MCM2 inhibitors by using structure-based virtual screening and surface plasmon resonance (SPR) assay. Furthermore, the efficacy of pixantrone targeting MCM2 in ovarian cancer was evaluated in vitro and in vivo. ResultsPixantrone was identified as a novel inhibitor of MCM2 by virtual screening. SPR binding affinity analysis confirmed the direct binding of pixantrone to MCM2 protein. Pixantrone significantly reduced the viability of ovarian cancer cells A2780 and SKOV3 in a dose- and time-dependent manner. In addition, pixantrone inhibited DNA replication, and induced cell cycle arrest and apoptosis in ovarian cancer cells via targeting MCM2. Knockdown of MCM2 could attenuate the inhibitory activity of pixantrone in ovarian cancer cells. Furthermore, pixantrone significantly suppressed ovarian cancer growth in the A2780 cell xenograft mouse model and showed favorable safety. ConclusionThese findings suggest that pixantrone may be a promising drug for ovarian cancer patients by targeting MCM2 in the clinic.

Ovarian cancer: Diagnosis and treatment strategies (Review).

Ovarian cancer is a malignant tumor that seriously endangers health. Early ovarian cancer symptoms are frequently challenging to detect, resulting in a large proportion of patients reaching an advanced stage when diagnosed. Conventional diagnosis relies heavily on serum biomarkers and pathological examination, but their sensitivity and specificity require improvement. Targeted therapy inhibits tumor growth by targeting certain characteristics of tumor cells, such as signaling pathways and gene mutations. However, the effectiveness of targeted therapy varies among individuals due to differences in their unique biological characteristics and requires individualized strategies. Immunotherapy is a promising treatment for ovarian cancer due to its long-lasting antitumor effect. Nevertheless, issues such as variable efficacy, immune-associated adverse effects and drug resistance remain to be resolved. The present review discusses the diagnostic strategies, rationale, treatment strategies and prospects of targeted therapy and immunotherapy for ovarian cancer.

Assessment of outcome of Ovarian Cancer Treatment; Retrospective cohort study

Assessment of outcome of Ovarian Cancer Treatment; Retrospective cohort study

Antibody-Drug Conjugates: The New Treatment Approaches for Ovarian Cancer.

Ovarian cancer (OC), accounting for approximately 200,000 deaths worldwide annually, is a heterogeneous disease showing major differences in terms of its incidence, tumor behavior, and outcomes across histological subtypes. In OC, primary chemotherapy, paclitaxel carboplatin, bevacizumab, and PARP inhibitors have shown prolonged progression-free survival and a favorable overall response rate compared to conventional treatments. However, treatment options for platinum-resistant recurrence cases are limited, with no effective therapies that significantly prolong the prognosis. Recently, mirvetuximab soravtansine, an alpha-folate receptor (FRα)-targeted antibody-drug conjugate (ADC), was approved by the US Food and Drug Administration for patients with FRα-positive recurrent epithelial OC (EOC). This approval was based on a Phase II study, which demonstrated its efficacy in such patients. ADCs comprise an antibody, a linker, and a payload, representing new concept agents without precedence. Advanced clinical studies are developing ADCs for patients with OC, targeting solid tumors such as gynecologic cancer. Ongoing clinical trials are evaluating ADCs targeting FRα and human epidermal growth factor receptor 2, trophoblast cell surface antigen-2, sodium-dependent phosphate transport protein 2B, and cadherin-6 in Phase II/III studies. In this review, we summarize the existing evidence supporting the use of ADCs in OC, discuss ongoing clinical trials and preclinical studies, and explore the potential of these innovative agents to address the challenges in OC treatment.

THUMPD3-AS1 inhibits ovarian cancer cell apoptosis through the miR-320d/ARF1 axis.

Ovarian cancer is one of the most common gynecologic malignancies that has a poor prognosis. THUMPD3-AS1 is an oncogenic long noncoding RNA (lncRNA) in several cancers. Moreover, miR-320d is downregulated and inhibited proliferation in ovarian cancer cells, whereas ARF1 was upregulated and promoted the malignant progression in epithelial ovarian cancer. Nevertheless, the role of THUMPD3-AS1 in ovarian cancer and the underlying mechanism has yet to be elucidated. Human normal ovarian epithelial cells (IOSE80) and ovarian cancer cell lines (CAVO3, A2780, SKOV3, OVCAR3, and HEY) were adopted for invitro experiments. The functional roles of THUMPD3-AS1 in cell viability and apoptosis were determined using CCK-8, flow cytometry, and TUNEL assays. Western blot was performed to assess the protein levels of ARF1, Bax, Bcl-2, and caspase 3, whereas RT-qPCR was applied to measure ARF1 mRNA, THUMPD3-AS1, and miR-320d levels. The targeting relationship between miR-320d and THUMPD3-AS1 or ARF1 was validated with dual luciferase assay. THUMPD3-AS1 and ARF1 were highly expressed in ovarian cancer cells, whereas miR-320d level was lowly expressed. THUMPD3-AS1 knockdown was able to repress cell viability and accelerate apoptosis of OVCAR3 and SKOV3 cells. Also, THUMPD3-AS1 acted as a sponge of miR-320d, preventing the degradation of ARF1. MiR-320d downregulation reversed the tumor suppressive function induced by THUMPD3-AS1 depletion. Additionally, miR-320d overexpression inhibited ovarian cancer cell viability and accelerated apoptosis, which was overturned by overexpression of ARF1. THUMPD3-AS1 inhibited ovarian cancer cell apoptosis by modulation of miR-320d/ARF1 axis. The discoveries might provide a prospective target for ovarian cancer treatment.