Cervical Cancer

Patients with HIV and HPV-16 infection exhibit a significantly higher rate of integrated HPV-16 infection, which is closely linked to HIV-induced immunosuppression, particularly the depletion of CD4+ T lymphocytes. This integration accelerates the progression of cervical lesions, increasing the risk of developing high-grade cervical intraepithelial neoplasia or cervical cancer. These findings underscore the need for targeted screening and therapeutic strategies in HIV-positive women to prevent HPV-related malignancies.

P1, N=200, Recruiting, BeiGene | Active, not recruiting --> Recruiting | N=37 --> 200 | Trial completion date: May 2026 --> Dec 2026 | Trial primary completion date: May 2025 --> Dec 2026

P=N/A, N=90, Not yet recruiting, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

P=N/A, N=700, Completed, Canadian Cancer Trials Group | Active, not recruiting --> Completed

Cox univariate and multivariate regression analyses indicated that DLEU1 was an independent risk factor for postoperative recurrence and metastasis in CC patients. Our findings suggest that serum exosome DLEU1 has certain clinical value for diagnosing, monitoring recurrence and metastasis, and evaluating CC prognosis.

Furthermore, nuclear survivin expression is very low in normal vulvar squamous epithelium and increases to become abundant in vulvar invasive squamous cell carcinoma (ISCC), conferring resistance to apoptosis in vulvar carcinogenesis. In this review, we discuss in detail the impact of survivin signaling on gynecological cancers and provide insight on its therapeutic and diagnostic potential, existing research gaps, and areas for future research.

The NPVs after 1-year cytology varied between 98.1% and 99.4%, warranting a return to routine screening. Altogether, DNA methylation-based triage strategies are recommended as they are discriminative for CIN3 and control the number of immediate colposcopy referrals.

This study provides novel insights into MGP regulation by demonstrating that YY1, GATA1, and C/EBPα are negative regulators of the MGP promoter, and DNA methylation may influence their activity. The dysregulation of these mechanisms in cancer should be further elucidated.

Rescue experiments revealed that the cancer-inhibiting effect of let-7c-5p in cervical cancer could be reversed by overexpressed CHD7. let-7c-5p regulates cell adhesion and attenuates cervical cancer migration and invasiveness by targeting CHD7. It indicates that the involvement of let-7c-5p/CHD7 axis is of significance in cervical cancer progression, which opens up new possibilities for us to develop novel clinical treatments for cervical cancer.

This study presents the first report on the discovery of a naturally occurring co-crystal of chrysin and oroxylin A and the involvement of ERKs and p38 of MAPK pathways in the induction of apoptosis in HeLa cells by the co-crystal. Our study sheds light on the development of a co-crystal of chrysin and oroxylin A in a specific ratio of 1:1 for combination therapy of the two APIs. The purified co-crystal was found to be more efficient compared to the compounds present individually. Further analysis of the physiochemical properties and molecular mechanisms of the isolated co-crystal in different cancer cells is warranted for its application in therapeutics.

This tool enables better patient management by allowing for timely interventions and personalized treatment strategies. Future research should focus on validating these findings in larger cohorts and integrating additional clinical parameters to enhance the predictive power of the ITS.

These findings underscore the critical role of CD19 within the tumor microenvironment, suggesting its potential as a biomarker and a therapeutic target in specific types of cancer.

Our results support that hucMSC-Ex alleviates LPS-induced cervical inflammation, possibly by inhibition of EMT.

P=N/A, N=1080, Active, not recruiting, Sun Yat-sen University | Recruiting --> Active, not recruiting | Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2024

P1/2, N=97, Active, not recruiting, NextCure, Inc. | Recruiting --> Active, not recruiting | N=209 --> 97

P2, N=40, Recruiting, ImmunityBio, Inc. | Active, not recruiting --> Recruiting | N=147 --> 40

Oral triapine is safe when given with cisplatin chemoradiation, convenient, bioavailable. Exposure is negatively impacted by smoking, and methemoglobin is a biomarker of exposure.

These results will help us elucidate the molecular factors influencing the progression of cervical precancer to cancer. Understanding the risk of progression of specific HPV types and sublineages may aid in the triage of positive patients, and better knowledge of the immune response may aid in developing and applying immunotherapies.

We then detected the epithelial-mesenchymal transition (EMT) markers [i.e., epithelial cadherin (E-cadherin), matrix metallopeptidase 9 (MMP9), vimentin, and snail family transcriptional repressor 1 (SNAIL)], phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK), to identify the potential mechanisms of AKF-PD. AKF-PD not only mitigates CP-induced AKI but also enhances the anti-cancer efficacy of CP. Our findings provide valuable insights into the treatment of NSCLC and may have clinical applications.

In summary, our study found that DHX34 is highly expressed in pan-cancer and has diagnostic and prognostic value. Targeting DHX34 may improve the therapeutic efficacy of immunotherapy and chemotherapy in a multitude of tumors.

PDT enhances cellular immune function in cervical HPV-infected patients by increasing CD4+ and CD8+ T-cells and reducing pro-inflammatory cytokines. These findings highlight the potential of PDT in modulating immune responses and improving therapeutic strategies for cervical HPV infection.

HPV type and Ct value on HPV-positive self-samples may be used for triage. The difference in the risk of CIN2+ in these groups appears sufficient to justify differential clinical management. A prospective study employing such triage to evaluate laboratory workflow, acceptability, and follow-up procedure and to optimise clinical performance seems warranted.

The study concludes that among ever-married women in the coastal districts of Bangladesh, there is a low prevalence of high-risk HPV. The predominant high-risk HPV genotypes identified were HPV 16, followed by HPV 66 and 68. These findings hold significant implications for policy makers, providing guidance for targeted screening strategies and vaccination programs.

Notable activities of linichlorin B, cynaropicrin, and aguerin B (with IC50 values of 13.67 μg/ml, 6.79 μg/ml, and 3.46 μg/ml, respectively) were detected in the PC-3 cell line; aguerin B demonstrated activity most comparable to the standard anticancer agent doxorubicin. Likewise, linichlorin B, aguerin B, and cynaropicrin demonstrated notable efficacy in the HeLa and MCF-7 cell lines, as reported by the American National Cancer Institute. Aguerin B, linichlorin B, and cynaropicrin are projected to serve as promising novel chemotherapeutic agents for cancer therapy.

Our findings highlight the potential of phosphoproteomics to identify clinically significant targets and pathways implicated in CCRT resistance. Our study also indicates that combination therapy could serve as an effective treatment strategy to improve the efficacy of patients undergoing CCRT.

P2, N=212, Active, not recruiting, Agenus Inc. | Trial primary completion date: Aug 2024 --> Jan 2025

P=N/A, N=1728, Recruiting, The University of Hong Kong | Not yet recruiting --> Recruiting

The findings of this study do not support the implementation of applicator tampon-based self-collection as a method for cytology-based cervical cancer screening.

P2, N=60, Not yet recruiting, MacroGenics

P=N/A, N=40, Completed, ARCAGY/ GINECO GROUP | Active, not recruiting --> Completed

P=N/A, N=8000, Active, not recruiting, The University of Texas Health Science Center, Houston | Recruiting --> Active, not recruiting | Trial completion date: Jul 2024 --> Aug 2025 | Trial primary completion date: Feb 2024 --> Aug 2025

P=N/A, N=2000, Enrolling by invitation, The University of Texas Health Science Center, Houston | Not yet recruiting --> Enrolling by invitation | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Jun 2025

Through modulating these tumour biological characteristics via ALDH1, bevacizumab increases the sensitivity of cervical carcinoma to cisplatin, suggesting that bevacizumab in combination with standard chemotherapy may represent a new strategy for overcoming drug resistance. Abbreviation: HPV, human papillomavirus; CSCs, cancer stem cells; ALDH1, aldehyde dehydrogenase 1; EMT, epithelial-mesenchymal transition; OD, optical density; qRT-PCR, RNA analysis by quantitative real-time polymerase chain reaction; RIPA, radioimmunoprecipitation assay; SDS-PAGE, sodium dodecyl sulphate-polyacrylamide gel electrophoresis; PVDF, polyvinylidene difluoride; ECL, electrochemiluminescence; NC, negative control; HE, haematoxylin and eosin; IHC, immunohistochemistry; DAB, 3, 3'-diaminobenzidine; IF, immunofluorescence; DAPI, 4,6-diamidino-2-phenylindole; VEGFA, vascular endothelial growth factor A; ROS, oxygen species; DFS, disease-free survival; OS, overall survival; HIF, hypoxia-inducible factor; PDGFs, platelet-derived growth factors; FGFs, fibroblast growth factors; PlGF, placenta growth factor; RTKs, receptor tyrosine kinases.

Further investigations are needed to unravel the specific target genes and pathways regulated by miR-182-5p. It is important to consider the emerging biologic and clinical implications of miR-182-5p in gynecologic cancers.

Both careHPV™ and Xpert® HPV have a good sensitivity and specificity as a POC cervical cancer screening method. These methods also hold potential for use on SCSs.

Unfortunately, the patient progressed rapidly during maintenance therapy when cadonilimab was replaced by sintilimab, the monoclonal antibody against PD-1, indicating the more powerful anti-tumor activity of dual blockade immunotherapy. To conclude, cadonilimab offers a promising and effective therapeutic approach for R/M CC. Notably, HER-2 is also expected to be a new reference target for cadonilimab therapy.

P2, N=26, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Oct 2025 --> Oct 2026

P2, N=134, Recruiting, Tianjin Medical University Cancer Institute and Hospital

Additionally, cell migration studies indicated that elevated expression of integrin α1, mediated by the TF:FVIIa/PAR2 pathway, was linked to enhanced cell migration, which could be inhibited by blocking integrin α1. This investigation uncovers a novel signaling pathway in HeLa cells, highlighting the significance of the TF:FVIIa:PAR2 axis in modulating integrins that are vital for cancer progression, thereby offering insights for potential targeted therapeutic approaches in cancer treatment.

Additionally, HPV16E4 mRNA expression was consistently detected in all LSIL samples, suggesting the presence of active viral replication. These findings might lead to further investigation into the interplay between HPV gene expression and host cell factors for targeted therapeutic strategies in cervical cancer management.

P=N/A, N=150, Recruiting, University of Aarhus | Not yet recruiting --> Recruiting | Trial completion date: Mar 2025 --> Jul 2025 | Trial primary completion date: Nov 2024 --> Jun 2025

P2, N=20, Recruiting, Shanghai Jiatan Pharmatech Co., Ltd | Trial completion date: Dec 2025 --> Dec 2026