Preliminary Analysis of Cervical Cancer Immunotherapy

Ma, Zhenqiang; Zou, Xinxin; Zhou, Yan; Chen, Caiyun; Chen, Yumei; Fu, Aizhen

doi:10.1097/coc.0000000000000950

Cited by 3 publications

(2 citation statements)

References 51 publications

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“…Inhibitors of CTLA‐4, such as ipilimumab and tremelimumab, have been extensively investigation in clinical trials, and completed phase I/II trials have shown potent immune activation in metastatic/recurrent cervical cancer. Additionally, other immune checkpoints, including OX40, GITR, TLR3, TIGIT, LAG3, TIM3, CD39, and A2AR, 326 , 327 as well as relevant agonist and antagonist antibodies, have been investigated in cervical cancer. However, none of them have been approved for use in the context of cervical cancer.…”

Section: Therapeutic Interventionsmentioning

confidence: 99%

Human papillomavirus associated cervical lesion: pathogenesis and therapeutic interventions

Ye,

Zheng,

et al. 2023

MedComm

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Human papillomavirus (HPV) is the most prevalent sexually transmitted virus globally. Persistent high‐risk HPV infection can result in cervical precancerous lesions and cervical cancer, with 70% of cervical cancer cases associated with high‐risk types HPV16 and 18. HPV infection imposes a significant financial and psychological burden. Therefore, studying methods to eradicate HPV infection and halt the progression of precancerous lesions remains crucial. This review comprehensively explores the mechanisms underlying HPV‐related cervical lesions, including the viral life cycle, immune factors, epithelial cell malignant transformation, and host and environmental contributing factors. Additionally, we provide a comprehensive overview of treatment methods for HPV‐related cervical precancerous lesions and cervical cancer. Our focus is on immunotherapy, encompassing HPV therapeutic vaccines, immune checkpoint inhibitors, and advanced adoptive T cell therapy. Furthermore, we summarize the commonly employed drugs and other nonsurgical treatments currently utilized in clinical practice for managing HPV infection and associated cervical lesions. Gene editing technology is currently undergoing clinical research and, although not yet employed officially in clinical treatment of cervical lesions, numerous preclinical studies have substantiated its efficacy. Therefore, it holds promise as a precise treatment strategy for HPV‐related cervical lesions.

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Section: Therapeutic Interventionsmentioning

confidence: 99%

Human papillomavirus associated cervical lesion: pathogenesis and therapeutic interventions

Ye,

Zheng,

et al. 2023

MedComm

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“…Cervical cancer, a gynecological malignancy, presents a high mortality rate globally and carries a poor prognosis in advanced stages. Each year, there are nearly 570,000 new cases of cervical cancer, resulting in over 300,000 female deaths [1]. Over the past decade, the introduction of novel therapies, such as anti-angiogenic therapy, immunotherapy, and targeted drugs, has contributed to improved diagnosis and treatment outcomes for cervical cancer [2].…”

mentioning

confidence: 99%

Aurora-A Regulating Cervical Cancer Invasion and Metastasis through ARPC4

Yue,

Mu,

Wang

et al. 2024

Preprint

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Objective：To investigate the impact of ARPC4 knockdown on cervical cancer cells with Aurora-A overexpression in terms of proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Methods:Gene expression profiling by RNA-seq, qPCR, and Western blotting were used to identify genes potentially regulated by Aurora-A. The proliferation, migration, and invasion abilities of the control and experimental groups were assessed using EDU fluorescence detection, cloning, scratch, and transwell assays. The molecular mechanism underlying ARPC4 regulation by Aurora-A was explored using Western blot analysis. Results:ARPC4 expression was found to decrease in Aurora-A knockdown cells and increase in Aurora-A overexpression cells. Patients with high ARPC4 expression had significantly shorter overall survival compared to those with low expression. Knockdown of ARPC4 counteracted the proliferation of cervical cancer cells induced by Aurora-A overexpression. Migration and invasion capabilities were suppressed in Aurora-A overexpression cell lines following ARPC4 knockdown. Aurora-A activation of the NF-κB p65 signaling pathway led to an upregulation of ARPC4 expression. Conclusion:ARPC4 expression is regulated by Aurora-A, and its knockdown mitigates the effects of Aurora-A overexpression on cervical cancer cells. Aurora-A activation of the NF-κB p65 signaling pathway upregulates ARPC4 expression, providing a potential therapeutic target for cervical cancer treatment.

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Discovery of the Inhibitor Targeting the SLC7A11/xCT Axis through In Silico and In Vitro Experiments

Yue,

Yin,

Feng

et al. 2024

IJMS

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In the development and progression of cervical cancer, oxidative stress plays an important role within the cells. Among them, Solute Carrier Family 7 Member 11 (SLC7A11/xCT) is crucial for maintaining the synthesis of glutathione and the antioxidant system in cervical cancer cells. In various tumor cells, studies have shown that SLC7A11 inhibits ferroptosis, a form of cell death, by mediating cystine uptake and maintaining glutathione synthesis. Additionally, SLC7A11 is also involved in promoting tumor metastasis and immune evasion. Therefore, inhibiting the SLC7A11/xCT axis has become a potential therapeutic strategy for cervical cancer. In this study, through structure-based high-throughput virtual screening, a compound targeting the SLC7A11/xCT axis named compound 1 (PubChem CID: 3492258) was discovered. In vitro experiments using HeLa cervical cancer cells as the experimental cell model showed that compound 1 could reduce intracellular glutathione levels, increase glutamate and reactive oxygen species (ROS) levels, disrupt the oxidative balance within HeLa cells, and induce cell death. Furthermore, molecular dynamics simulation results showed that compound 1 has a stronger binding affinity with SLC7A11 compared to the positive control erastin. Overall, all the results mentioned above indicate the potential of compound 1 in targeting the SLC7A11/xCT axis and treating cervical cancer both in vitro and in silico.

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Preliminary Analysis of Cervical Cancer Immunotherapy

Cited by 3 publications

References 51 publications

Human papillomavirus associated cervical lesion: pathogenesis and therapeutic interventions

Human papillomavirus associated cervical lesion: pathogenesis and therapeutic interventions

Aurora-A Regulating Cervical Cancer Invasion and Metastasis through ARPC4

Discovery of the Inhibitor Targeting the SLC7A11/xCT Axis through In Silico and In Vitro Experiments

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