ABSTRACT Background Folate receptor α (FRα) is a glycosylphosphatidylinositol‐anchored protein that facilitates folate transport and has emerged as a promising therapeutic target for ovarian cancer, particularly due to its association with tumor progression. This Phase I study investigated the safety, tolerability, pharmacokinetics, and preliminary efficacy of mirvetuximab soravtansine (MIRV), an antibody‐drug conjugate targeting folate receptor α (FRα), in Chinese patients with FRα‐overexpressed platinum‐resistant ovarian cancer. Methods This study enrolled 19 Chinese patients with previously treated FRα‐overexpressed ovarian cancer in the dose escalation phase (5 mg/kg, n = 4; 6 mg/kg, n = 3) and dose expansion phase (n = 12). MIRV was administered in escalating doses from 5 to 6 mg/kg (adjusted ideal body weight), following a 3 + 3 dose‐escalation design. The trial is registered with chinadrugtrials.org.cn (CTR20211876). Results Median treatment exposure were 9.9 weeks for the 5 mg/kg cohort (n = 4) and 13.1 weeks for the 6 mg/kg cohort (n = 15). The most common grade ≥ 3 adverse events were decreased platelet count (21.1%), decreased lymphocyte count (15.8%), and anemia (15.8%). The plasma concentration‐time and pharmacokinetic profiles of MIRV and the total antibody were generally comparable after the first and third doses. Pharmacokinetic analysis revealed a median time to maximum concentration (Tmax) of 3.33 h, mean terminal half‐life (T1/2) of 118 h, and geometric mean maximum concentration (Cmax) of 137.07 μg/mL. MIRV exposures were comparable to those reported in Caucasian patients. No anti‐drug antibodies were detected. Among 15 efficacy‐evaluable patients with high‐grade serous ovarian cancer, the objective response rate was 26.7%, with partial responses in four patients and stable disease in seven patients. Conclusions MIRV showed anticipated pharmacokinetics, safety, tolerability, and efficacy profiles in Chinese patients with FRα‐positive platinum‐resistant ovarian cancers, supporting its potential as a targeted therapeutic agent for this patient population. Trial Registration The trial is registered with chinadrugtrials.org.cn (CTR20211876)

Cervical cancer (CC) remains one of the most prevalent gynecological malignancies worldwide, with patients diagnosed at advanced stages often facing poor prognoses due to the lack of effective therapeutic options. ADARB1 (Adenosine Deaminase Acting on RNA 1), an RNA-editing enzyme, has been implicated in the pathogenesis of various cancers; however, its functional role in cervical cancer remains largely unexplored. In this study, we observed a significant downregulation of ADARB1 expression in both cervical cancer tissues and cell lines, which was associated with unfavorable clinical outcomes. Functional assays revealed that ADARB1 overexpression markedly inhibited the proliferation, migration, invasion, and glycolytic activity of cervical cancer cells, whereas ADARB1 knockdown exerted the opposite effects. Mechanistically, we found that ADARB1 mRNA binds to HMGB1 (High Mobility Group Box 1) protein and regulates its expression via the ubiquitin-proteasome pathway, thereby modulating the malignant phenotype of cervical cancer. Notably, ectopic expression of HMGB1 partially reversed the suppressive effects of ADARB1 on cell proliferation and glycolysis. Further investigation revealed that HMGB1 interacts with PFKFB3 (6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase 3), a key regulatory enzyme in glycolysis, and modulates its protein stability, suggesting the presence of a critical HMGB1/PFKFB3 signaling axis in cancer metabolism. ADARB1 exerts its anti-tumor effects primarily through the HMGB1/PFKFB3 pathway. Collectively, these findings identify ADARB1 as a novel tumor suppressor in cervical cancer and a promising therapeutic target for clinical intervention.

Objective To investigate the influencing factors for asymptomatic venous thromboembolism(VTE)in patients with ovarian clear cell carcinoma(OCCC)after primary surgery and to construct a predictive model for postoperative asymptomatic VTE.Methods The patients who underwent primary surgical treatment at Zhongnan Hospital of Wuhan University from 2013 to 2023 were enrolled as the research subjects and the clinical data were retrospectively collected.Univariate analysis and multivariate Logistic regression analysis were employed to identify independent influencing factors for postoperative VTE and to construct a nomogram model.The model's discrimination,calibration,and clinical utility were evaluated using,receiver operating characteristic(ROC)curves with area under the curve(AUC),calibration curves and decision curve analysis(DCA).Additionally,multivariable Cox regression was used to assess the impact of VTE on patients'overall survival(OS).Results A total of 172 OCCC patients were included.The incidence of postoperative asymptomatic VTE was 26.16%.Multivariable Logistic regression indicated that elevated preoperative D-dimer levels[OR=1.002,95%CI(1.001,1.004)]served as an independent risk factor for postoperative asymptomatic VTE.Conversely,higher preoperative hemoglobin levels[OR=0.849,95%CI(0.767,0.912)]and prolonged prothrombin time[OR=0.096,95%CI(0.013,0.329)]were identified as independent protective factors.The predictive model yielded an AUC of 0.989[95%CI(0.969,1.000)].The calibration curve demonstrated high consistency between the predicted probability and actual risk,while the decision curve showed significant net benefit.Multivariable Cox regression revealed that postoperative asymptomatic VTE was an independent risk factor for OS[adjusted HR=3.770,95%CI(1.112,12.821)].Conclusion Postoperative asymptomatic VTE significantly impairs the long-term survival of OCCC patients.The predictive model based on preoperative hematological parameters enables individualized risk stratification,facilitating the identification of high-risk populations and guiding early screening and intervention.

Sirtuin 2 (SIRT2) is one of the key members of sirtuins family that plays important role in regulating many physiological processes. Recent evidences have revealed that SIRT2 is associated with the development, progression and metastasis of ovarian cancer. In this study, guided by an in-depth analysis of the clinical characteristics of the expression pattern of SIRT2 in ovarian cancer patients, the first SIRT2-targeted hydrophobic tagging (HyT) degraders have been developed. These acyl thiourea degraders exhibited remarkable anti-proliferative activity in several ovarian cancer cells. Among them, the most effective compound II-6 exhibited excellent anti-tumor activity both in vitro and in vivo (half maximal inhibitory concentration (IC50) = 0.002 (0.001 }mol/L). In addition, II-6 was found to effectively suppress cancer cell proliferation and migration, as well as cell cycle arrest and apoptosis. Moreover, further investigation revealed that compound II-6 indirectly induced DNA damage through the H4K20me2/53BP1 pathway by degradation of SIRT2. The study not only exemplifies the advantage of the novel HyT degradation strategy but also prove the great potential of SIRT2 as a promising target for drug development of ovarian cancer. (c) 2026 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

The phase 3 COMPASSION-16 trial demonstrates significant progression-free survival (PFS) and overall survival (OS) benefits with cadonilimab plus standard therapy in patients with persistent, recurrent, or metastatic cervical cancer. This analysis aims to assess efficacy outcomes in patient subgroups of COMPASSION-16. The dual primary endpoints of COMPASSION-16 are PFS, assessed by the blinded independent central review (BICR) according to RECIST version 1.1, and OS. The secondary endpoint is objective response rate. In this subgroup analysis, the PFS, OS and objective response rate are evaluated in subgroups including bevacizumab use, prior concurrent chemoradiotherapy, PD-L1 combined positive score (CPS), metastatic disease at baseline, platinum use, and age. With median follow-up of 25.6 months, hazard ratios (HRs) for PFS favour cadonilimab group in all subgroups. Moreover, the addition of cadonilimab is also associated with prolonged overall survival. This subgroup analysis confirms that improvements in progression-free and overall survival are consistent with the primary results of the COMPASSION-16 study across diverse patient profiles.

Ovarian cancer is a highly lethal gynecological malignancy that poses a significant threat to women's health. Current treatments for patients with clinical recurrence and drug resistance are limited, underscoring the urgent need for new therapeutic strategies. SIRT2, one subtype of sirtuin protein family, has been shown to promote tumor cell proliferation, migration, and invasion by regulating multiple signaling pathways through deacetylation. In this study, we discovered that knockdown of SIRT2 significantly inhibited the migration and invasion of ovarian cancer cells. To develop targeted therapies, we designed and synthesized a series of SIRT2-targeted PROTACs based on the small molecule inhibitor Tenovin-6. These PROTACs exhibited potent SIRT2 degradation capability and significant anti-proliferative activity in several ovarian cancer cell lines. Among them, W10 demonstrated the most potent anti-proliferative activity both in vitro and in vivo, with an IC50 value of 0.08 ± 0.04 μmol/L and a selectivity index (SI) of 33.00. W10 significantly suppressed clonogenic formation and migration, induced cell cycle arrest, and promoted apoptosis. Mechanistically, W10 inhibited the AKT/mTOR signaling pathway by indirectly degrading SIRT2 and blocking downstream protein phosphorylation, thereby disrupting the signaling cascade and suppressing tumor development.

BACKGROUND:Ovarian clear cell cancer (OCCC) is a pathological type of ovarian cancer. OCCC responds poorly to platinum-based chemotherapy drugs and immunotherapy. Currently, there is a lack of targeted drugs for OCCC. It is very urgent to find new therapeutic targets for OCCC. METHODS:We used data from the eQTLGen consortium and deCODE, combined with large Genome-Wide Association Study (GWAS) cohort data, to perform drug target Mendelian randomization (MR) analysis. Colocalization analysis was used to identify target genes. Then, we analyzed single-cell sequencing data from the GEO database, combing with gene enrichment analysis to explore possible molecular mechanisms. Drug screening and molecular docking verified the medicinal value of the targets. RESULTS:Three genes were selected in the MR analysis. Colocalization supported two of them, PPP1R14A and PTGS2. Single-cell sequencing analysis showed that these genes were related to tumor immunity. Drug prediction and molecular docking showed that PTGS2 had druggable potential. CONCLUSIONS:This study identified two potential drug targets for OCCC. These drug targets may be relevant to tumor immunotherapy. However, further studies are necessary to confirm these findings and clarify the underlying mechanisms.

BACKGROUND:Cervical cancer remains a significant health burden for women worldwide, with persistent high-risk HPV infection being a major etiological factor. Despite treatment advances, prognosis for recurrent or metastatic disease remains poor. Pyroptosis, a form of programmed cell death, plays a dual role in tumor immunity, but its implications in cervical cancer are not fully elucidated. This study aims to systematically characterize pyroptosis-related genes (PRGs) in cervical cancer and explore their prognostic and therapeutic relevance. METHODS:Multi-omics data from TCGA and GEO databases were integrated to analyze genetic variations, expression patterns, and prognostic significance of 52 PRGs in cervical cancer. Consensus clustering was used to identify PRG subtypes. A prognostic risk score model was constructed using LASSO-Cox regression based on differentially expressed genes (DEGs). Functional validation was performed via in vitro and in vivo experiments, including Western blot, CCK-8, colony formation, transwell assays, and a subcutaneous tumor model. Single-cell RNA sequencing data (GSE171894, GSE168652) were analyzed to explore LAG3 expression in the tumor immune microenvironment. RESULTS:Two distinct PRG subtypes were identified, with subtype A showing immune activation features. A five-gene prognostic signature (GNAZ, LAG3, IL-1β, CA2, SPRR3) effectively stratified patients into high- and low-risk groups. Low LAG3 expression was associated with poor prognosis. Functional experiments demonstrated that LAG3 overexpression suppressed cervical cancer cell proliferation, migration, and tumor growth, while its knockdown promoted malignant phenotypes. Single-cell analysis revealed high LAG3 expression in Treg and CD8⁺ T cells, suggesting its role in immune regulation. CONCLUSION:This study establishes a novel PRG-based prognostic model and highlights LAG3 as a key tumor suppressor and immune regulator in cervical cancer. These findings provide insights into the interplay between pyroptosis and antitumor immunity, supporting LAG3 as a potential therapeutic target for cervical cancer immunotherapy.

ObjectiveAsian females with ovarian cancer have different clinicopathological characteristics compared with other races. However, an effective prognostic prediction tool is lacking. The goal of our study was to develop and evaluate nomograms for estimating overall survival and cancer-specific survival in Asian patients with ovarian cancer.MethodsWe extracted data from 2010 to 2018 in the Surveillance, Epidemiology, and End Results database, focusing on Asian/Pacific Islander females that had been diagnosed with epithelial ovarian cancer. To find prognostic factors, least absolute shrinkage and selection operator Cox regression and multivariate Cox regression analyses were used. Based on the outcomes, nomograms were then constructed. Numerous techniques, such as the C-index, calibration plots, decision curve analysis, and risk subgroup stratification, were used to assess the performance of the nomograms.ResultsNomograms were created to evaluate overall survival and cancer-specific survival rates over three and five years. The C-indices for overall survival and cancer-specific survival in the training cohort were 0.768 and 0.778, respectively. The C-indices for overall survival and cancer-specific survival in the validation cohort were 0.804 and 0.812, respectively. The calibration plots showed that the nomogram forecasts and actual survival results agreed. Additionally, the decision curve analysis curves indicated that the nomogram outperformed the American Joint Commission on Cancer staging system in terms of predictive accuracy.ConclusionNomograms and a risk classification system were created to forecast the overall survival and cancer-specific survival of Asian females with ovarian cancer. The nomograms and risk stratification system have the potential to provide valuable assistance in making future clinical decisions.

Cervical cancer is a significant threat to women's health, and its incidence in China has been increasing in recent years. Treating advanced and recurrent cervical cancer has become increasingly challenging, highlighting the urgent need to identify new therapeutic targets for this disease. SIX1 is associated with cell proliferation, metastasis, and chemoresistance in various human malignancies. SIX1 overexpression in cervical cancer tissues has been linked to increased clinical stage and lymph node metastasis; however, the regulatory function of SIX1 in cervical cancer remains largely unexplored. In this study, we found that SIX1 promotes cervical cancer cell proliferation, invasion, and migration by enhancing glucose metabolism. Additionally, SIX1 was shown to influence the glycolytic process in cervical cancer by upregulating GLUT1, PFK1, PGK1, ENO1, and PKM2 expression. Furthermore, we identified a binding site for SIX1 in the ENO1 promoter region, demonstrating that SIX1 has a regulatory effect. These results suggest that SIX1 regulates proliferation and glucose metabolism in cervical cancer cells by promoting the transcription of key glycolytic enzymes, such as ENO1. Understanding this regulatory mechanism is crucial for identifying potential therapeutic targets for cervical cancer.

Backgrounds Advanced elderly ovarian cancer patients often experience adverse postoperative outcomes and prognosis. Currently, although multiple frailty assessment tools and nutritional serum biomarkers have been employed for risk assessment and outcome prediction, there remains no consensus on the optimal "gold standard" predictive tool. Methods A retrospective study was conducted to collect general information, clinical pathological data, and follow-up information of 117 advanced elderly ovarian cancer patients aged ≥65, who underwent ovarian tumor cytoreductive surgery at Wuhan University Zhongnan Hospital between 2012 and 2021. The 5-MFI was used to assess frailty. Preoperative albumin was used to assess nutritional status.The MFI-Alb model was developed as a composite predictor integrating 5-MFI and albumin.Cox regression and logistic regression were used to investigate predicting factors.The predictive performance of the models was evaluated using AUC and ROC curves. Results Logistic regression analysis showed that 5-MFI and MFI-Alb were independent predictors for hospital stay and OS. The AUC for the MFI-Alb predicting hospital stay was 0.742 (95% CI 0.646-0.837), for 5-MFI was 0.697 (95% CI 0.603-0.791), and for preoperative albumin was 0.583 (95% CI 0.471-0.694), with the MFI-Alb model outperforming the other two. In terms of OS, the AUC for the MFI-Alb model predicting OS was 0.746 (95% CI 0.659-0.834), for 5-MFI was 0.734 (95% CI 0.650-0.818), and for preoperative albumin was 0.520 (95% CI 0.415-0.626), again showing superior predictive performance for the MFI-Alb model. Conclusions The MFI-Alb model, which integrates frailty and nutritional status, exhibits superior predictive performance for both hospital stay length and OS compared to using 5-MFI or albumin alone.

TikTok is one of the most popular video-sharing social media platforms currently, with an increasing number of users posting and searching for cervical cancer-related videos. However, the quality and reliability of these videos have not been thoroughly evaluated. We conducted searches using #cervical cancer on TikTok, reviewed all included videos, and identified seven themes related to cervical cancer for analysis. We assessed the quality and reliability of the videos using the JAMA score and Modified DISCERN score. We also conducted intergroup comparative analysis of video quality and reliability for different thematic contents. A total of 100 Chinese-language videos related to cervical cancer were collected. Seven themes were established based on content, including cervical cancer patient experiences, cause of disease, symptoms, HPV-related topics, cancer treatment, laboratory and imaging examinations, and prognosis. The median JAMA score for all videos was only 1 (0, 3), and the median Modified DISCERN score was also only 1 (0, 4), indicating unsatisfactory results. When comparing video scores by different thematic contents, both scores showed statistically significant differences between groups (p < 0.001). Overall, the quality and reliability of Chinese-language cervical cancer videos on TikTok are low. Healthcare professionals should strive to improve video quality and reliability when publishing content, and patients should maintain a cautious attitude when searching for related content.

Cervical cancer possesses high morbidity and mortality rates, and a comprehensive understanding of its molecular underpinnings is essential for advancing clinical management strategies. The innate immune sensor STING, which activates type I interferon signaling, plays a pivotal role in enhancing anti-tumor activity. Despite increased attention to STING's involvement in cervical cancer, the regulatory mechanisms governing its protein homeostasis remain poorly understood. In this study, it is found that the BAG2-STUB1 complex regulates ubiquitin proteasomal degradation of STING, which affects the development of cervical cancer. Mechanistically, BAG2 inhibits ubiquitination of STING and stabilizes it by interacting with STING. Specifically, BAG2 inhibits STUB1 from attaching the K48-linked ubiquitin chains at K338 and K370 of STING by forming a complex with STUB1. Functionally, enhanced BAG2 expression suppresses cervical cancer progression by activating the type I interferon pathway in a STING-dependent manner. Notably, clinical cervical cancer samples revealed a positive correlation between BAG2 and STING levels, with low BAG2 expression is strongly linked to advanced disease and poor prognosis in cervical cancer. Collectively, these findings elucidate the molecular mechanism by which the BAG2-STUB1 complex regulates STING homeostasis, underscoring BAG2's potential as a diagnostic biomarker and therapeutic target in cervical cancer.

Objective We aimed to evaluate the ability of Adult Comorbidity Evaluation 27 (ACE-27) to predict perioperative outcomes and survival in elderly women with advanced epithelial ovarian cancer (AEOC) undergoing cytoreductive surgery. Methods We collected patients with AEOC in our hospital between January 1, 2012 and January 1, 2021. Patients younger than 65 years old or those with non-epithelial ovarian cancer were excluded. ACE-27 was applied retrospectively to assess comorbidities in the selected patients, who were then classified into two groups based on their ACE-27 scores: low ACE-27 score group (none to mild) and high ACE-27 score group (moderate to severe). Results A total of 222 elderly women with AEOC were included, of whom 164 patients accepted debulking surgery. Among those who have undergone surgery, Clavien–Dindo grade III + perioperative complications or unintended intensive care unit (ICU) admission occurred more often in patients of high ACE-27 score group, with statistically significant difference (odds ratio [OR]: 4.21, 95% confidence interval [CI], 1.28–14.35, p = 0.018). Further stratified analyses by age, BMI, FIGO stage and pathology also prove that OS of patients graded severe was shorter than patients graded none to moderate in cohort of age < 70, BMI < 25 kg/m 2 , FIGO III stage and pathology of serous, respectively. Kaplan–Meier survival curves analyzed by log-rank test showed that the overall survival (OS) of patients with severe comorbidities were shorter than with none to moderate (HR 3.25, 95%CI 1.55–6.79, p = 0.002). Conclusions Our findings demonstrate the ability of ACE-27 to predict grade III + perioperative complications or unintended ICU admission and survival in elderly patients with AEOC. This highlights the possibility for ACE-27 to play an instrumental role in identifying AEOC patients who are more susceptible to adverse surgical outcomes and have a poor survival rate and assisting in decisions regarding treatment.

BACKGROUND:Cervical cancer is one of the most common gynecological cancers. Accumulated evidence shows that long non-coding RNAs (lncRNAs) play essential roles in cervical cancer occurrence and progression, but their specific functions and mechanisms remain to be further explored. METHODS:The RT-qPCR assay was used to detect the expression of NEAT1 in cervical cancer tissues and cell lines. CCK-8, colony formation, flow cytometry, western blotting, and Transwell assays were used to evaluate the impact of NEAT1 on the malignant behavior of cervical cancer cells. Glucose consumption, lactate production, ATP levels, ROS levels, MMP levels, and the mRNA expressions of glycolysis-related genes and tricarboxylic acid cycle-related genes were detected to analyze the effect of NEAT1 on metabolism reprograming in cervical cancer cells. The expressions of PDK1, β-catenin and downstream molecules of the WNT/β-catenin signaling pathway in cervical cancer cells and tissues were detected by western blotting, RT-qPCR, immunofluorescence and immunohistochemistry assays. RESULTS:This study investigated the role and possible molecular mechanism of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in cervical cancer. Our results showed that NEAT1 was highly expressed in cervical cancer tissues and cell lines. Downregulation of NEAT1 inhibited the proliferation, migration, invasion and glycolysis of cervical cancer cells, while overexpression of NEAT1 led to the opposite effects. Mechanistically, NEAT1 upregulated pyruvate dehydrogenase kinase (PDK1) through the WNT/β-catenin signaling pathway, which enhanced glycolysis and then facilitated cervical cancer metastasis. Furthermore, NEAT1 maintained the protein stability of β-catenin but did not affect its mRNA level. We also excluded the direct binding of NEAT1 to the β-catenin protein via RNA pull-down assay. The suppressive impact of NEAT1 knockdown on cell proliferation, invasion, and migration was rescued by β-catenin overexpression. The WNT inhibitor iCRT3 attenuated the carcinogenic effect induced by NEAT1 overexpression. CONCLUSION:In summary, these findings indicated that NEAT1 may contribute to the progression of cervical cancer by activating the WNT/β-catenin/PDK1 signaling axis.

BACKGROUND:Cadonilimab is a bispecific antibody targeting PD-1 and CTLA-4, which has shown substantial clinical benefits in advanced cervical cancer. In the COMPASSION-16 trial, we aimed to evaluate the addition of cadonilimab to first-line standard chemotherapy in persistent, recurrent, or metastatic cervical cancer. METHODS:In this randomised, double-blind, multicentre, placebo-controlled phase 3 trial, women aged 18-75 years across 59 clinical sites in China with previously untreated persistent, recurrent, or metastatic cervical cancer were randomly assigned (1:1) to receive cadonilimab (10 mg/kg) or placebo plus platinum-based chemotherapy with or without bevacizumab every 3 weeks for six cycles, followed by maintenance therapy every 3 weeks for up to 2 years. Randomisation was performed centrally through an interactive web-response system. Stratification factors were the use of bevacizumab (yes or no) and previous concurrent chemoradiotherapy (yes or no). The dual primary outcomes were progression-free survival as assessed by blinded independent central review and overall survival in the full analysis set. This study is registered with ClinicalTrials.gov, NCT04982237; the study has completed enrolment and is ongoing for treatment and follow-up. FINDINGS:445 eligible women were enrolled between Sept 11, 2021, and June 23, 2022. Median progression-free survival was 12·7 months (95% CI 11·6-16·1) in the cadonilimab group and 8·1 months (7·7-9·6) in the placebo group (hazard ratio 0·62 [95% CI 0·49-0·80], p<0·0001); median overall survival was not reached (27·0 months to not estimable) versus 22·8 months (17·6-29·0), respectively (hazard ratio 0·64 [0·48-0·86], p=0·0011). The most common grade 3 or higher adverse events were decreased neutrophil count, decreased white blood cell count, and anaemia. INTERPRETATION:The addition of cadonilimab to first-line standard chemotherapy significantly improved progression-free survival and overall survival with a manageable safety profile in participants with persistent, recurrent, or metastatic cervical cancer. The data support the use of cadonilimab plus chemotherapy as an efficacious first-line therapy in persistent, recurrent, or metastatic cervical cancer. FUNDING:Akeso Biopharma.

The development of effective drugs for cervical cancer is urgently required because of its high mortality rate and the limited treatment options. Herein, we report the design, synthesis, and evaluation of a series of novel and effective Hsp90-targeting PROTACs. These compounds exhibited potent anti-proliferative activity against cervical cancer cells with low IC50 values. Compound lw13 effectively degraded Hsp90 at a concentration of only 0.05 μM. In addition, it can inhibit the metastasis of cancer cells and induce significant cell cycle arrest and apoptosis. Furthermore, lw13 demonstrated remarkable antitumor activity both in vitro and in vivo, and has a synergistic effect in combination with cisplatin. Moreover, lw13 can prevent the activation of the HER2/AKT/mTOR signaling pathway by indirectly reducing the levels of HER2 and AKT. This study paves the way for cancer treatment and provides valuable insights into the combination therapy of cervical cancer.

AbstractPurpose: Immune checkpoint inhibitors (ICI) have been a potential treatment option for patients with cervical cancer in several clinical studies. We investigated the safety and efficacy of cadonilimab, a bispecific antibody targeting PD-1 and CTLA-4, plus standard therapy for the first-line treatment of R/M CC (recurrent and/or metastatic cervical cancer). Patients and Methods: Eligible patients were assigned to 3 cohorts: cohort A-15 (cadonilimab 15 mg/kg every 3 weeks (Q3W) plus chemotherapy), cohort A-10 (cadonilimb 10 mg/kg Q3W plus chemotherapy), and cohort B-10 (cadonilimab 10 mg/kg Q3W plus chemotherapy and bevacizumab). They received the corresponding treatments until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision. The primary objective was safety; the secondary endpoints included objective overall response (ORR), duration of response, disease control rate, progression-free survival, and overall survival. This study is registered with ClinicalTrials.gov (NCT04868708). Results: As of February 13, 2023, treatment-related adverse events (TRAE) occurred in 45 (100.0%) patients. Grade ≥3 TRAEs were reported in 33 (73.3%) patients. Immune-related adverse events (irAE) occurred in 29 (64.4%) patients and grade ≥3 irAEs were observed in 9 (20.0%) patients. Seven (15.6%) of 45 patients permanently discontinued cadonilimab treatment due to TRAEs. One death due to hemorrhagic shock occurred in cohort B-10. Among 44 patients who underwent at least one post-baseline tumor assessment, the ORR was 66.7% in cohort A-15, 68.8% in cohort A-10, 92.3% in cohort B-10, and 79.3% in cohorts A-10 and B-10 combined. Conclusions: Cadonilimab combined with standard therapy was acceptable, with encouraging antitumor activity in patients with R/M CC.

Objective To explore the value of blood inflammatory load in predicting overall survival of elderly patients with epithelial ovarian cancer(EOC).Methods Elderly patients with EOC were selected,and their clinical data and peripheral blood parameters were collected.We constructed an inflammation-related blood scoring system using univariate and multivariate Cox regression analysis.The Kaplan-Meier method was used for survival analysis.We used Cox proportional hazards analysis to identify the independent prognostic factors.A nomogram model was constructed based on independent prognostic factors,and the receiver operating characteristic curve,C-index,and calibration curve were used to evaluate the model.Results Patients with high blood inflammatory load had worse prognosis(P=0.002).Compared with the low inflammatory load group,patients with high inflammatory load had later clinical stages and larger ascites volume(P<0.05).Cox regression analysis showed that ACCI,CA125,residual lesions,and blood score were independent factors affecting overall survival(P<0.05).Conclusion The blood inflammatory load is the biomarker for the prognosis of elderly patients with EOC.Scoring the inflammatory load in the blood can assist in efficacy monitoring and treatment intervention of ovarian cancer patients.