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Table of Content

    08 November 2025, Volume 52 Issue 11 Previous Issue   
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    Original article
    Effects of circRNA-15430 targeting miR-10 on proliferation and invasion of gastric cancer cells
    Zhang Shuai, Liu Liangliang, Huang Di, Sheng Ru, Qi Mengyao, Li Shuguang
    2025, 52 (11):  673-679.  doi: 10.3760/cma.j.cn371439-20241203-00116
    Abstract ( 25 )   HTML ( 5 )   PDF (2514KB) ( 5 )   Save

    Objective To explore the effect of circular RNA (circRNA)-15430 on the proliferation and invasion of gastric cancer cells by regulating mircoRNA-10 (miR-10). Methods The relative expression levels of circRNA-15430 and miR-10 in gastric epithelial cell line GES-1 and four gastric cancer cell lines (GTL16, NUGC-3, MGC803, Snu-1) were detected by real-time fluorescence quantitative PCR. The gastric cancer cell line GTL16 were taken, and the cells were divided into the gastric cancer cell (GC) group, the gastric cancer cell+circRNA-15430-NC (CN) group, the gastric cancer cell+circRNA-15430 inhibitor (CI) group, the gastric cancer cell +circRNA-15430 agonist (CM) group, the gastric cancer cell+miR-10-NC (MN) group, the gastric cancer cell+miR-10 agonist (MM) group, the gastric cancer cell+miR-10 inhibitor (MI) group, and the gastric cancer cell+circRNA-15430 agonist+miR-10 inhibitor (UI) group. Cell proliferation was detected by the CCK-8 method, and cell invasion was detected by the Transwell chamber method. The dual-luciferase reporter gene assay was used to confirm the interaction between circRNA-15430 and miR-10. Results Real-time fluorescence quantitative PCR showed that the relative expression levels of circRNA-15430 in GES-1 and four types of gastric cancer cells were 1.00±0.00, 0.31±0.02, 0.62±0.04, 0.59±0.03 and 0.63±0.05, respectively, with a statistically significant difference (F=334.70, P<0.001); The relative expression levels of miR-10 in GES-1 and four types of gastric cancer cells were 1.00±0.00, 1.80±0.18, 1.53±0.14, 1.49±0.13 and 1.51±0.15, respectively, with a statistically significant difference (F=27.52, P<0.001). The relative expression levels of circRNA-15430 in the four types of gastric cancer cells were all lower than those in GES-1 cells, and the relative expression levels in NUGC-3, MGC803, and Snu-1 cells were all higher than those in GTL16 cells (all P<0.05). The relative expression levels of miR-10 in the four types of gastric cancer cells were all higher than those in GES-1 cells (all P<0.05), and the relative expression levels in NUGC-3, MGC803, and Snu-1 cells were all lower than those in GTL16 cells (all P<0.05). Therefore, GTL16 cells were selected as the experimental cells for this experiment. The results of the cell proliferation and invasion assay showed that the cell proliferation rates of the GC group, CN group, CI group and CM group were (47.06±4.61) %, (47.04±4.63) %, (68.61±6.59) % and (28.52±2.16) %, respectively, with a statistically significant difference (F=71.02, P<0.001). The invasion numbers were 195.57±20.04, 195.35±20.08, 316.86±32.20 and 169.04±16.11, respectively, with a statistically significant difference (F=50.18, P<0.001). The cell proliferation rate and invasion number in the CI group were both higher than those in the GC group and CN group, while the cell proliferation rate and invasion number in the CM group were both lower than those in the GC group, CN group and the CI group (all P<0.05). The cell proliferation rates of the MN group, MM group, and MI group were (47.18±4.62) %, (68.68±6.36) % and (28.55±2.12) %, respectively. The invasion numbers were 195.78±20.07, 316.90±32.21 and 169.10±16.15, respectively. There were statistically significant differences in cell proliferation rates and the invasion numbers among the GC group, MN group, MM group and MI group (F=73.79, P<0.001; F=50.08, P<0.001). The cell proliferation rate and invasion number in the MM group were both higher than those in the GC group and MN group, while the cell proliferation rate and invasion number in the MI group were both lower than those in the GC group, MN group and the MM group (all P<0.05). The cell proliferation rate in the UI group was (20.31±1.11) %, and the invasion number was 107.51±10.02. There were statistically significant differences in cell proliferation rates and invasion numbers among the CM group, MI group and UI group (F=39.06, P<0.001; F=36.63, P<0.001). The cell proliferation rate and invasion number in the UI group were both lower than those in the CM group and MI group (all P<0.05). The results of the dual-luciferase reporter gene assay showed that transfection with circRNA-15430 could significantly reduce the luciferase activity of miR-10-3'-UTR-WT (t=21.22, P<0.001), but had no significant effect on the mutant gene (t=0.85, P=0.413). Conclusions circRNA-15430 can effectively inhibit the proliferation and invasion of gastric cancer cells, and its mechanism may be related to the targeted inhibition of miR-10.

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    METTL3 inhibits the proliferation and migration of liver cancer cells by regulating the m6A modification of RAB5C
    Ma Lijun, Ji Haitao, Qu Xiaowei, Wang Yanfeng, Gao Xiaowei, Han Jiming
    2025, 52 (11):  680-688.  doi: 10.3760/cma.j.cn371439-20250513-00117
    Abstract ( 26 )   HTML ( 3 )   PDF (4832KB) ( 7 )   Save

    Objective To explore the effects and possible mechanisms of methyltransferase-like protein 3 (METTL3) on the proliferation and migration of liver cancer cells by regulating the stability of RAB5C. Methods The expression of RAB5C in liver cancer tissues and its relationship with clinicopathological characteristics were were analyzed using the UALCAN database; The liver cancer cells of the logarithmic growth phase were divided into the following groups: si-NC group (transfected with a blank fragment), si-RAB5C-1 group (RAB5C silenced), si-RAB5C-2 group (RAB5C silenced), si-NC+over-NC group (transfected with a blank fragment+a blank vector), si-METTL3+over-NC group (METTL3 silenced+a blank vector), and si-METTL3+over-RAB5C group (METTL3 silenced+RAB5C overexpression vector); RAB5C-WT+si-NC group (RAB5C wild-type vector+control vector) and RAB5C-MUT+si-METTL3 group (RAB5C mutant vector+METTL3 silenced); EdU experiment was conducted to detect cell proliferation ability; Transwell experiment was conducted to detect cell migration ability; Flow cytometry was used to detect the level of cell apoptosis; GEPIA database was used to analyze the correlation between METTL3 and RAB5C expression; SARMP database was used to predict the m6A modification site in RAB5C; The targeted regulation relationship between METTL3 and RAB5C was identified by using dual luciferase reporter gene assay and Me-RIP assay. Results Analysis of the UALCAN database showed that the expression levels of RAB5C mRNA in normal tissues (n=50) and liver cancer tissues (n=371) were 54.1 (44.9, 63.1) and 93.5 (67.1, 120.0), respectively, with a statistically significant difference (χ2=0.01, P<0.001). The expression levels of RAB5C mRNA in patients with non-metastatic lymph nodes (n=252) and metastatic lymph nodes (n=4) were 93.9 (65.1, 120.4) and 117.5 (100.3, 142.9), respectively; the expression levels in patients with TP53 mutation (n=105) and non-mutation (n=105) were 100.2 (80.5, 133.1) and 84.7 (62.3, 115.9), respectively, with statistically significant differences (χ2=0.72, P=0.020; χ2=0.74, P=0.010). The EdU assay results indicated that the cell proliferation rates of the HepG2 cells in the si-NC group, si-RAB5C-1 group, and si-RAB5C-2 group were (39.3±2.93)%, (19.98±1.77)%, and (19.98±2.46)%, respectively, with a statistically significant difference (F=63.01, P<0.001), and the cell proliferation rates of the si-RAB5C-1 group and si-RAB5C-2 group were both lower than that of the si-NC group (both P<0.05). The results of the Transwell assay showed that the migration numbers of HepG2 cells in the si-NC group, si-RAB5C-1 group, and si-RAB5C-2 group were 94.2±1.2, 26.1±0.5, and 25.1±0.6, respectively, with a statistically significant difference (F=87.26, P<0.001), and the number of cell migration in the si-NC group was higher than that in the si-RAB5C-1 group and the si-RAB5C-2 group (both P<0.05). The results of flow cytometry showed that the apoptosis rates of HepG2 cells in the si-NC group, si-RAB5C-1 group and si-RAB5C-2 group were (7.18±1.04)%, (12.56±1.50)%, and (11.68±1.54)%, respectively, with a statistically significant difference (F=13.09, P=0.007), and the apoptosis rates of the si-RAB5C-1 group and the si-RAB5C-2 group were both higher than that of the si-NC group (both P<0.05). GEPIA and SARMP database analysis showed that the expression of METTL3 was positively correlated with that of RAB5C (r=0.13, P=0.002), and there were multiple m6A modification sites and corresponding m6A binding site motifs in RAB5C. The results of the MeRIP-qPCR experiment showed that the relative expression level of RAB5C in the HepG2 cell of si-NC group was 1.00±0.11, which was higher than that in the si-METTL3 group (0.28±0.18), with a statistically significant difference (t=6.89, P=0.002). The results of the dual-luciferase reporter gene assay showed that compared with the RAB5C-WT+si-NC group (1.00±0.16), silencing the expression of METTL3 in HepG2 liver cancer cells could significantly inhibit the luciferase activity of the wild-type RAB5C promoter (0.50±0.12), with a statistically significant difference (t=4.26, P=0.010); while compared with the RAB5C-WT+si-NC group (1.00±0.03), si-METTL3 treatment had no significant effect on the luciferase activity of the mutant RAB5C promoter (0.97±0.01) (t=1.53, P=0.200). The results of EdU assay, Transwell experiment, and flow cytometry showed that there were statistically significant differences in cell proliferation, migration, and apoptosis among the si-NC+over-NC group, si-METTL3+over-NC group, and si-METTL3+over-RAB5C group (all P<0.05). Compared with the si-METTL3+over-NC group, there were statistically significant differences in cell proliferation, migration, and apoptosis in the si-METTL3+over-RAB5C group (all P<0.05). Conclusions METTL3 may regulate the expression of RAB5C through mediated m6A modification, thus inhibiting the occurrence and development of liver cancer.

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    Study on dose optimization strategy of dynamic intensity-modulated radiotherapy based on the inner edge tangent field for the target area after breast-conserving surgery for left-sided breast cancer
    Zhao Biao, Zhu Yupu, Zhang Yating, Yuan Meifang, Li Han, Yang Yi, Sun Chaoxi
    2025, 52 (11):  689-694.  doi: 10.3760/cma.j.cn371439-20250507-00118
    Abstract ( 23 )   HTML ( 2 )   PDF (1439KB) ( 4 )   Save

    Objective To explore the dose optimization strategy of dynamic intensity-modulated radiotherapy (dIMRT) based on the inner edge tangential field (IETF) for the target area after breast-conserving surgery for left-sided breast cancer. Methods The localization CT and target organ at risk (OAR) data of 36 patients with left-sided breast cancer treated with breast-conserving surgery and postoperative radiotherapy in the Department of Radiotherapy of Yunnan Cancer Hospital from August 2023 to October 2024 were retrospectively selected. Two dIMRT schedules, conventional tangential field (CTF)-dIMRT and IETF-dIMRT, were designed for each patient; The target dose and the OAR dose of the two groups were counted and analyzed. Results For CTF-dIMRT and IETF-dIMRT, the D98% of the target area were (47.36±0.88) and (47.61±0.81) Gy, and the D50% were (52.08±0.23) and (52.01±0.22) Gy, the conformity index (CI) were 0.82±0.03 and 0.84±0.03, with statistically significant differences (t=-3.45, P=0.001; t=2.28, P=0.029; t=-6.24, P<0.001). The D2% were (53.83±0.33) and (53.89±0.42) Gy, the homogeneity index (HI) were 0.12±0.02 and 0.12±0.02, with no statistically significant difference (t=-1.11, P=0.276; t=1.89, P=0.067). For CTF-dIMRT and IETF-dIMRT, the V5 of left lung were (35.40±7.77) % and (31.44±6.01) %, the V20 were (12.69±2.84) % and (11.48±2.22) %, the Dmean were (8.15±1.42) and (7.39±1.13) Gy, with statistically significant differences (t=6.92, P<0.001; t=6.79, P<0.001; t=9.10, P<0.001). The heart Dmean were (4.99±1.15) and (4.29±1.00) Gy, the right lung Dmean were (1.24±0.12) and (1.15±0.11) Gy, the right breast Dmean were (2.34±1.01) and (3.26±1.54) Gy, the spinal cord D2 were (1.26±0.13) and (1.22±0.12) Gy, with statistically significant differences (t=7.88, P<0.001; t=6.66, P<0.001; t=-6.85, P<0.001; t=2.76, P=0.009). Conclusions Both IETF-dIMRT and CTF-dIMRT can fully meet clinical requirements. Compared with CTF-dIMRT, IETF-dIMRT after breast-conserving surgery for left-sided breast cancer has more benefits in terms of target dose and OAR protection.

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    Diagnostic value of MRI combined with serum LRG1 and LOXL2 for prostate cancer
    Ye Rui, Chen Zhen, Hao Ningning, Li Rongrong
    2025, 52 (11):  695-699.  doi: 10.3760/cma.j.cn371439-20250123-00119
    Abstract ( 18 )   HTML ( 2 )   PDF (942KB) ( 2 )   Save

    Objective To explore the diagnostic value of MRI combined with serum levels of leucine-rich α2 glycoprotein 1 (LRG1) and lysyl oxidase like-2 protein (LOXL2) for prostate cancer. Methods A total of 84 patients with prostate cancer who were treated at the 900th Hospital of PLA Joint Logistic Support Force from January 2021 to December 2023 were selected as the research subjects (prostate cancer group). Meanwhile, 59 patients diagnosed with benign prostate lesions by pathology during the same period were selected as the control group. All subjects underwent multiparametric MRI examination. The levels of serum LRG1 and LOXL2 in the two groups of patients were determined by enzyme linked immunosorbent assay (ELISA). Receiver operator characteristic (ROC) curve was used to analyze the diagnostic value of MRI, levels of serum LRG1, LOXL2 and prostate specific antigen (PSA) for prostate cancer. Results The volume transfer constant (Ktrans) of the control group and the prostate cancer group were (0.09±0.03) and (0.13±0.04)/min, respectively, the rate constant (Kep) were (0.48±0.11) and (0.53±0.12)/min, respectively, and the apparent diffusion coefficient (ADC) were (1.16±0.15)×10-3 and (0.92±0.13)×10-3 mm2/s, respectively, with statistically significant differences (t=6.50, P<0.001; t=2.54, P=0.012; t=10.20, P<0.001). The serum LRG1 levels of the prostate cancer group and the control group were (115.48±15.61) and (92.51±14.34) ng/ml, respectively, the LOXL2 levels were (6.79±1.15) and (5.21±0.93) ng/ml, respectively, and the PSA levels were 16.05 (12.23, 22.89) and 6.04 (2.62, 12.04) ng/ml, respectively, with statistically significant differences (t=8.96,P<0.001; t=8.73, P<0.001; Z=7.02, P<0.001). ROC curve analysis showed that, the area under the curve (AUC) of MRI, serum LRG1, LOXL2 and PSA levels in the diagnosis of prostate cancer were 0.826, 0.844, 0.829, and 0.845, respectively. The AUC of the combined diagnosis of prostate cancer by MRI, serum levels of LRG1 and LOXL2 was 0.929, and the combined diagnostic efficacy was better than that of MRI (Z=4.51, P<0.001), serum LRG1 (Z=3.65, P<0.001), LOXL2 (Z=3.91, P<0.001), and PSA (Z=2.30, P=0.022) alone. Conclusions MRI combined with the levels of serum LRG1 and LOXL2 has a relatively high diagnostic efficacy for prostate cancer.

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    Relationship between miR-506-3p and immune microenvironment characteristics and platinum chemotherapy sensitivity in patients with epithelial ovarian cancer
    Liu Hui, Ruan Jianhui, Huang Yuan, Xiong Yanli, Zhou Xiaoli
    2025, 52 (11):  700-707.  doi: 10.3760/cma.j.cn371439-20241216-00120
    Abstract ( 13 )   HTML ( 2 )   PDF (959KB) ( 1 )   Save

    Objective To analyze the relationship between miR-506-3p and immune microenvironment characteristics and platinum chemotherapy sensitivity in patients with epithelial ovarian cancer (EOC). Methods A total of 87 EOC patients admitted to General Hospital of Central Theater Command, People's Liberation Army of China from June 2021 to June 2023 were selected as the study subjects. According to the chemotherapy efficacy, the patients were divided into a sensitive group (n=57) and a drug-resistant group (n=30). The expression of miR-506-3p in EOC tissues and adjacent tissues was compared. The relationships between the expression of miR-506-3p in EOC tissues and the clinicopathological characteristics, immune microenvironment characteristics [levels of T cell subsets CD4+, CD8+, helper T (Th) 17 cells, and regulatory T (Treg) cells, as well as the ratio of CD4+/CD8+ and the ratio of Treg cells /Th17 cells] and chemotherapy sensitivity to platinum drugs were analyzed. The relationship between the platinum chemotherapy sensitivity in EOC patients of the sensitive group and the drug-resistant group and the clinicopathological characteristics, immune microenvironment characteristics, and miR-506-3p expression was analyzed. A generalized additive model (GAM) was used to analyze the relationship between the expression of miR-506-3p and immune microenvironment-related indicators. A multivariate logistic regression model was used to conduct an independent correlation analysis and subgroup internal correlation analysis of miR-506-3p expression and the platinum chemotherapy sensitivity. A restricted cubic spline logistic regression model was established to analyze the dose-response relationship between miR-506-3p expression and the platinum chemotherapy sensitivity in patients with EOC. Results The expression level of miR-506-3p in the EOC tissues (0.33±0.09) was significantly lower than that in the adjacent tissues (1.12±0.40), with a statistically significant difference (t=19.05,P<0.001). According to the average expression level of miR-506-3p (0.33), the EOC patients were divided into a high-expression group (n=42) and a low-expression group (n=45). There were statistically significant differences in the immune microenvironment characteristics [CD8+ T cells (t=2.91, P=0.006), Th17 cells (t=3.69,P=0.001), Treg cells (t=3.12,P=0.003), Treg cells/Th17 cells ratio (t=4.23,P<0.001)] and platinum chemotherapy sensitivity (χ2=18.32,P<0.001) between the low-expression group and the high-expression group. Compared with the sensitive group, the proportions of age≥55 years old (χ2=4.74, P=0.029), FIGO stage Ⅲ-Ⅳ (χ2=6.11, P=0.013), BRCA mutation rate (χ2=9.47, P=0.002), T cell subsets CD8+ level (t=5.57, P<0.001), Th17 cell level (t=6.50, P<0.001) in the drug-resistant group were significantly increased, while T cell subsets CD4+ level (t=2.48, P=0.015), CD4+/CD8+ ratio (t=3.36, P=0.001), Treg cells level (t=5.26, P<0.001), Treg cells/Th17 cells ratio (t=4.39, P<0.001), and miR-506-3p expression level (t=8.99, P<0.001) were significantly decreased, with statistically significant differences. GAM analysis results showed that the immune microenvironment indicators CD4+ T cells level (F=7.34,P<0.001), CD8+ T cells level (F=4.58, P<0.001), CD4+/CD8+ ratio (F=2.03, P=0.005), Th17 cells level (F=6.17, P<0.001), Treg cells level (F=1.98, P=0.009), and Treg cells/Th17 cells ratio (F=2.71, P=0.002) were all correlated with the expression of miR-506-3p. The results of multivariate logistic regression analysis showed that the expression of miR-506-3p in EOC tissues was independently correlated with platinum chemotherapy sensitivity (P<0.001). Subgroup analysis showed that in EOC patients with different ages and maximum diameter of residual lesion, the relationship between miR-506-3p expression in EOC tissues and platinum chemotherapy sensitivity was stable, and there was no interaction between subgroups. Restricted cubic spline model analysis showed that the risk of chemotherapy resistance to platinum drugs decreased with the increase of miR-506-3p expression level. Conclusions The expression level of miR-506-3p in EOC tissues is related to the immune microenvironment of patients and can regulate the balance of CD4+ and CD8+ T cells as well as Th17 and Treg cells. The expression of miR-506-3p is independently and stably associated with the sensitivity of EOC patients to platinum-based chemotherapy. Its increase can reduce the risk of chemotherapy resistance and is expected to become a potential biomarker for evaluating the immune status of EOC patients and predicting the efficacy of platinum-based chemotherapy.

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    Review
    Research progress of long non-coding RNA DLEU1 in malignant tumors
    Sun Mingzhu, Liu Yanquan, Sun Lei, Tang Huanwen
    2025, 52 (11):  708-713.  doi: 10.3760/cma.j.cn371439-20250523-00121
    Abstract ( 12 )   HTML ( 2 )   PDF (836KB) ( 2 )   Save

    Long non-coding RNA DLEU1 has emerged as a novel key molecule in pan-cancer research, potentially playing a critical role in regulating the occurrence and progression of malignant tumors. Although studies on DLEU1 remain limited, recent researches have confirmed its aberrant expression in various malignancies. DLEU1 can regulate the malignant phenotype of tumor cells through competitive endogenous RNA mechanisms, epigenetic regulation, and transcriptional feedback loops, including proliferation, migration, invasion, and chemoresistance, which are closely associated with poor prognosis. Additionally, its enrichment in exosomes suggests its potential as a diagnostic biomarker. Systematic analysis and exploration of the expression regulation and mechanism of action of DLEU1 in various malignant tumors can deeply understand the biological mechanisms such as the spatio-temporal heterogeneity, targeted treatment strategies, and interaction with the microenvironment of DLEU1 in malignant tumors, providing reference and guidance for precise tumor treatment and basic research applications based on non-coding RNA.

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    Research progress of patient-derived organoid models in metastatic cancer
    Yu Ziwei, Zhuang Qingchun, Sun Jing, Li Xinyu, Sha Dan
    2025, 52 (11):  714-719.  doi: 10.3760/cma.j.cn371439-20250901-00122
    Abstract ( 12 )   HTML ( 2 )   PDF (823KB) ( 1 )   Save

    Patient-derived organoids (PDOs) are self-assembling, microscopic three-dimensional structures cultivated in vitro from stem cells. They can highly recapitulate the structural, physiological, and genetic characteristics of the original tissue and demonstrate a high correlation with patients' clinical efficacy. In recent years, PDOs models have emerged as an ideal tool for investigating the mechanisms of tumor metastasis and developing corresponding therapeutic strategies. Further exploration of the application and latest research progress regarding PDOs models in various types of metastatic cancers will provide a critical theoretical foundation for advancing precision anti-tumor treatment strategies.

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    Mechanisms of radionuclide therapy for tumors and research advances in gliomas
    Liao Zhipeng, He Yonglin, Du Aichao, Pan Yawen
    2025, 52 (11):  720-725.  doi: 10.3760/cma.j.cn371439-20250530-00123
    Abstract ( 16 )   HTML ( 3 )   PDF (807KB) ( 7 )   Save

    Glioma, particularly glioblastoma, is a type of highly malignant central nervous system tumors with extremely poor prognoses. In recent years, radionuclides have demonstrated unique advantages in the diagnosis and treatment of gliomas. Radionuclide therapy enables precise tumor cell eradication through the emission of radioactive particles, and further achieves precise radiotherapy by crossing the blood-brain barrier through diverse delivery systems. However, at present, there is a lack of research on precise targeting of glioma stem cells and the combined strategy of radiotherapy and immunotherapy. As research continues to advance, radionuclide therapy holds promise for breaking through the existing therapeutic limitations and offering new directions for the comprehensive treatment of gliomas.

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    Research progress on combined radiotherapy, chemotherapy, and immunotherapy for cervical cancer
    Ma Yongjia, Peng Siyu, Sun Pengfei
    2025, 52 (11):  726-731.  doi: 10.3760/cma.j.cn371439-20250619-00124
    Abstract ( 15 )   HTML ( 2 )   PDF (803KB) ( 1 )   Save

    In clinical studies of cervical cancer, the combination of radiotherapy, chemotherapy, and immunotherapy has yielded certain results. Programmed death-1/programmed death-ligand 1 inhibitors have also demonstrated positive results in multiple clinical trials. Novel immunotherapies such as human papillomavirus peptide vaccines, DNA vaccines, tumor-infiltrating lymphocyte therapy, and bispecific antibodies have been applied in the treatment of recurrent or metastatic cervical cancer, demonstrating significant anti-tumor activity, the potential to reshape the immune microenvironment, adaptability to personalized treatment, and synergistic effects when combined with multi-modal therapies. A deeper exploration of the synergistic mechanisms of combined therapy regimens and the application and development limitations of various therapies in cervical cancer treatment can provide insights for further optimizing treatment strategies for cervical cancer.

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