Precision medicine for cervical cancer

Manrriquez, Erica; Zakhour, Mae; Salani, Ritu

doi:10.1097/gco.0000000000000755

Cited by 13 publications

(11 citation statements)

References 27 publications

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“…By enrolling all cells from diverse individual patients, we successfully identi ed nine cell types based on their marker genes. The composition of these cell types varied across different individuals, indicating the need for precision medicine in cervical cancer [59]. Differences have also been documented across three stages in disease diagnostics [39,60], which were consistent with the result in our study.…”

Section: Discussionsupporting

confidence: 91%

Insights into tumor microenvironment and HPV integrations in cervical cancer pathogenesis revealed by single-cell transcriptome data

Peng,

Zeng,

Wang

et al. 2024

Preprint

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Background HPV infection is prevalent among women, and can lead to severe diseases. This study leverages single-cell RNA-sequencing (scRNA-seq), a cutting-edge technology that allows for cellular-level exploration, to investigate the relationship between cellular heterogeneity and HPV integrations in cervical histopathology.Methods We applied scRNA-seq to examine heterogeneity across normal and three disease stages patients with normal, high-grade squamous intraepithelial lesions (HSIL), microinvasive carcinoma (MIC), and cervical squamous epithelium carcinoma cancer (CSCC) tissues. A pipeline was developed to detect the HPV integration events from scRNA-seq data in this study.Results Our findings revealed an increase in the proportion of squamous epithelial cells and a decrease in the proportion of columnar epithelial cells in the disease progress from normal to CSCC. We identified HPV genes expressed differentially across normal and three disease stages. Notably, we observed HPV integration events occurring more frequently in squamous epithelial cells at single-cell level. An increasing trend in the ratio of HPV-integrated cells was observed in the disease progress from normal tissue to CSCC, which eventually plateaued. We identified several genes, including EGR1, S100A11, S100A8, KRT5, RPL34, ATP1B1, RPS4X and EEF2 that were frequently integrated by HPV across patients. In contrast, genes such as PAN3, BABAM2, SPEN, TCIM-SIRLNT, TEX41-PABPC1P2 and KCNV1-LINC01608 showed frequent integration events across cells. Some of these genes exhibited significant expression differences between tumor and normal squamous epithelial cells. KRT5, ATP1B1, RPS4X, PAN3 and SPEN were novel recurrent HPV-integrated genes we observed at the patient or cell level in this study. Furthermore, we found that HPV genes from various HPV types demonstrated integration preferences in different samples and disease stages.Conclusions These findings uncovered the intricate heterogeneity across normal and three disease stages caused by varying degrees of HPV infection, offering a valuable single-cell perspective on the mechanism of HPV-induced cervical cancer and its clinical relevance.

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Section: Discussionsupporting

confidence: 91%

Insights into tumor microenvironment and HPV integrations in cervical cancer pathogenesis revealed by single-cell transcriptome data

Peng,

Zeng,

Wang

et al. 2024

Preprint

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“…The role of a combination of cisplatin plus gemcitabine is still evolving [ 10 , 11 ]. The role of targeted therapy and precision therapy/radiobiotherapy in the future needs to be defined and likely to improve the outcomes [ 12 , 13 ].…”

Section: Methodsmentioning

confidence: 99%

The Influence of Patient and System Factors on the Radiotherapy Treatment Time in the Treatment of Non-metastatic Cervical Cancer Patients in a Rural and Resource-Lean State’s Safety-Net Hospital: Benefits of Strategic Planning

Vijayakumar¹,

Nittala²,

Duggar³

et al. 2023

Cureus

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Objective To decrease radiotherapy treatment time (RTT), measured from the day of initiation of radiotherapy to the day of its completion, specific strategies were initiated in early 2020 in the only academic safety-net medical center in a rural, resource-lean state. The factors that can succeed and those that need further improvements were analyzed in this initial assessment phase of our efforts to shorten the RTT. Methods This is an analysis of 28 cervix cancer patients treated with magnetic resonance imaging (MRI)-guided brachytherapy (February 2020-November 2021). The relationship between independent and dependent variable were analyzed by simple linear regression, and p-values ≤ 0.05 were considered statistically significant. SPSS software version 28.0 (IBM, Armonk, NY, USA) was used for statistical analysis. Results Two RTT groups (≤ 60 (32.1%) vs . > 60 days {67.9%}) with median RTT of 68 days (range, 51 to 106 days) were analyzed. Caucasians represented 66.7% of the RTT ≤ 60 days group. Four ‘issues’ were identified that increased the RTT: non-compliance, learning curve (early days of implementation of MRI-guided brachytherapy in the department), stage IV comorbidities, and with more than one issue mentioned; 77.8% with no issues had ≤ 60 days RTT vs . 26.3% for the > 60 days group. The breakdown of the no-issues factor by calendar year showed the RTT of ≤ 60 days was achieved higher in 2021 (85.7% vs. 20.0%; p=0.023) compared to 2020. For this entire cohort, the RTT of ≤ 60 days was achieved higher in 2021 (50.0% vs. 8.3%; p=0.019) compared to 2020. Data also showed improvement in RTT of ≤ 60 days for every sequential six months. ‘Non-compliance’ and ‘learning curve’ were the most important factors among patients having the longest RTTs. Conclusion The RTT can be further decreased. As a result of this preliminary analysis of the our strategic planning approach of ‘circular’ “See it,” “Own it,” “Solve it,” and “Do it” and go back to the first step again, we plan to implement the following strategies in the immediate future to shorten the RTTs further and, in turn, improve our overall outcomes (local/regional control, disease-free survival, and overall survival): (a) Interdigitate MRI-guided brachytherapy during external beam radiotherapy (EBRT); patients who can not get the interdigitated brachytherapy procedures performed during the course of EBRT for any reason will receive two brachytherapy procedures per week; (c) attempt to add a cervix cancer care navigator to our staff to help patients having social issues, thus leading to compliance problems; (d) finally, in a year or two after these new strategic implementations, the RTT data will be reanalyzed.

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“…However, cervical cancer‐related mortality remained relatively stable over the same time. This lack of improvement in mortality corresponds to those with advanced and distant metastasis in which limited treatment fails to produce curative outcomes 2 . To avoid recurrence after surgery and reduce the survival rate of patients, most patients will receive clinical chemotherapy drugs such as cisplatin, Taxol, Gemcitabine, and immunotherapy developed in recent years, but often causes serious side effects 3,4 .…”

Section: Introductionmentioning

confidence: 99%

“…lack of improvement in mortality corresponds to those with advanced and distant metastasis in which limited treatment fails to produce curative outcomes. 2 To avoid recurrence after surgery and reduce the survival rate of patients, most patients will receive clinical chemotherapy drugs such as cisplatin, Taxol, Gemcitabine, and immunotherapy developed in recent years, but often causes serious side effects. 3,4 Therefore, the continuous search for effective natural drugs with low side effects is still the goal of current efforts.…”

mentioning

confidence: 99%

Induction of immunogenic cell death effect of licoricidin in cervical cancer cells by enhancing endoplasmic reticulum stress‐mediated high mobility group box 1 expression

Chiou

Hsieh

et al. 2023

Environmental Toxicology

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Licoricidin (LCD) is an activity compound of the roots of Glycyrrhiza uralensis, which has therapeutic efficacy, including anti‐virus, anti‐cancer, and enhanced immunity in Traditional Chinese Medicine. Herein, this study aimed to clarify the effect of LCD on cervical cancer cells. In the present study, we found that LCD significantly inhibited cell viability via inducing cell apoptosis and companies with cleaved‐PARP protein expression and caspase‐3/‐9 activity. Cell viability was markedly reversed these effects by pan‐caspase inhibitor Z‐VAD‐FMK treatment. Furthermore, we showed that LCD‐induced ER (endoplasmic reticulum) stress triggers upregulating the protein level of GRP78 (Bip), CHOP, and IRE1α, and subsequently confirmed the mRNA level by quantitative real‐time polymerase chain reaction. In addition, LCD exhibited the release of danger‐associated molecular patterns from cervical cancer cells, such as the release of high‐mobility group box 1 (HMGB1), secretion of ATP, and exposure of calreticulin (CRT) on the cell surface, which led to immunogenic cell death (ICD). These results provide a novel foundation that LCD induces ICD via triggering ER stress in human cervical cancer cells. LCD might be an ICD inducer of immunotherapy in progressive cervical cancer.

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Precision medicine for cervical cancer

Cited by 13 publications

References 27 publications

Insights into tumor microenvironment and HPV integrations in cervical cancer pathogenesis revealed by single-cell transcriptome data

Insights into tumor microenvironment and HPV integrations in cervical cancer pathogenesis revealed by single-cell transcriptome data

The Influence of Patient and System Factors on the Radiotherapy Treatment Time in the Treatment of Non-metastatic Cervical Cancer Patients in a Rural and Resource-Lean State’s Safety-Net Hospital: Benefits of Strategic Planning

Induction of immunogenic cell death effect of licoricidin in cervical cancer cells by enhancing endoplasmic reticulum stress‐mediated high mobility group box 1 expression

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